s-1-(combination) and Neutropenia

We performed a meta-analysis oriented at the risk of leucopenic complications associated with S-1-based regimens.. The studies that were granted eligibility for inclusion include randomized phase II and III trials of patients with solid tumors on S-1; that entailed details of events of febrile neutropenia, all-grade and high-grade neutropenia and leucopenia.. After rejecting ineligible studies, a total of 28 clinical trials were elected eligible for further quantitative analysis. The RR of febrile neutropenia, all-grade and high-grade neutropenia for S-1 vs.non fluoropyrimidine controls was 0.27 [95% CI 0.16, 0.46; P < 0.0001] 0.69 [95% CI 0.58, 0.81; P < 0.00001] and 0.47 [95% CI 0.32, 0.70; P = 0.0002], correspondingly; while The RR of all-grade and high-grade leucopenia for S-1 vs.non fluoropyrimidine controls was 0.60 [95% CI 0.46, 0.79; P = 0.0002] and 0.34 [95% CI 0.14, 0.79; P = 0.01], respectively.. The risk of febrile neutropenia, all-grade and high-grade neutropenia and leucopenia is less in S-1-based therapy than in non fluoropyrimidine regimens; yet comparable to the risk associated with infusional 5FU or capecitabine-based regimens.

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Combinations; Humans; Neoplasms; Neutropenia; Oxonic Acid; Pyrimidines; Randomized Controlled Trials as Topic; Risk; Tegafur

Two pivotal phase II studies of S-1 in advanced gastric cancer showed response rates of 44% and 49%, and the overall survival time was 207 and 250 days, respectively. The response rate of S-1 exceeded the response rates of other approved drugs, and was comparable to that of combination chemotherapies such as 5-fluorouracil (5-FU) plus cisplatin (CDDP). These data suggested that S-1 could be used as a first-line drug for gastric cancer with a great advantage in quality of life (QOL), because it is an oral drug and can be used at an outpatient clinic. The overall incidences of adverse reactions in the phase II studies were 74.3%, and that of grade 3 or worse were 14.9%. The main adverse reactions were myelosuppression and GI toxicities. As hematological toxicity was more common than other oral fluoropyrimidine derivatives such as UFT, a careful hematological monitoring is necessary. To confirm the survival benefit of S-1 in advanced gastric cancer, a phase III trial of S-1 vs 5-FU vs CDDP plus irinotecan (CPT-11) has been conducted by the Japan Clinical Oncology Group (JCOG), and these results have been awaited. Furthermore, the combination of S-1 with CDDP, CPT-11 or taxane for the treatment of gastric cancer is feasible and active, and phase III studies of S-1 vs several combination therapies including S-1 are also in progress. The effect of S-1 in adjuvant setting is also promising. Currently, a phase III study of surgery alone vs S-1 in patients with a curative resection of gastric cancer has been developed. Further therapeutic benefits are also expected by combining S-1 with other chemotherapeutic agents such as molecular targeted agents.

Topics: Administration, Oral; Anemia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Leukopenia; Neutropenia; Oxonic Acid; Quality of Life; Stomach Neoplasms; Stomatitis; Tegafur

The S-1 +biweekly docetaxel (DOC) combination therapy was evaluated for advanced or recurrent gastric cancer patients. This combination therapy was evaluated in vitro using the nude rat-gastric cancer xenograft system. S-1 alone or DOC alone showed antitumor activity, and the antitumor activity was synergistic when two drugs were combined. In clinical settings, the schedule was S-1 80 mg/m2 (day 1-14, orally) and DOC (day 1 and day 15, intravenously) followed by a 2-week rest. In phase I study, the dose of DOC was evaluated, and a recommended dose for phase II was determined as 35 mg/m2. The entry for phase II study was completed, and the preliminary results of 33 patients showed the response rate of 21.2%. The incidence of more than grade 3 adverse effects was 29%(neutropenia, leukocytopenia, anorexia and mucositis). The S-1 +biweekly DOC combination therapy can be a candidate for outpatient chemotherapy for advanced or recurrent gastric cancer.

Topics: Animals; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Docetaxel; Drug Combinations; Humans; Leukopenia; Neoplasm Transplantation; Neutropenia; Oxonic Acid; Quality of Life; Randomized Controlled Trials as Topic; Rats; Rats, Nude; Stomach Neoplasms; Stomatitis; Taxoids; Tegafur

Chemotherapy for colorectal cancer is now improving rapidly due to new drugs like oxaliplatin and molecular targeting drugs. The key drug, however, is still 5-fluorouracil (5-FU). S-1 is an oral 5-FU anti-tumor drug that combines three pharmacological agents: tegafur, 5-chloro-2,4-dihydroxypyridine, which inhibits dihydropyrimidine dehydrogenase activity, and potassium oxonate, which reduces gastrointestinal toxicity. The results of the phase II study suggested that S-1 as a single agent was active against metastatic colorectal cancer: CR rate was 36-40% and MST was about one-year. Toxicity was all tolerable. Clinical trials of S-1 with oxaliplatin or CPT-11 combination chemotherapy are ongoing in Japan. S-1 with molecular targeting drugs will also be studied. Therefore, S-1 is expected to play an important part in chemotherapy for colorectal cancer.

Topics: Administration, Oral; Anorexia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leukopenia; Neutropenia; Oxonic Acid; Survival Rate; Tegafur

A combination therapy of irinotecan hydrochloride (CPT-11) with continuous intravenous infusions of (infusional) 5-fluorouracil (5-FU) and Leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns on safety and convenience have prompted the development of new oral fluoropyrimidine derivatives which improved regimens. Yamada et al conducted a phase I study to assess the maximum tolerated dose and recommended dose of S-1 combined with CPT-11. The study recommended that 150 mg/m2 of CPT-11 be given on day 1 and 80 mg/m2 of S-1 daily on days 1 to 14 every 3 weeks. Recently, several phase I/II studies assessed the efficacy and safety of the combined therapy with S-1 and CPT-11 in patients with advanced colorectal cancer. Some of the studies which were ongoing assessed a tri-weekly schedule regimen. Our results showed that S-1 plus CPT-11 was very effective, with a response rate of 63% and PFS of 8 months. Toxicity was generally mild and manageable on an outpatient basis. The current evidence showed that a combination of S-1 and CPT-11 was more convenient and easier to administer than a combination of CPT-11 plus infusional 5-FU and LV. It will be essential to prove that the combination of S-1 plus CPT-11 can replace the combination of infusional 5-FU and LV plus CPT-11 without negatively affecting efficacy and toxicity.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Remission Induction; Survival Rate; Tegafur

The combination with cisplatin (CDDP) and 5-FU is considered the first choice chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a modulation of tegafur developed in Japan, is an active agent for HNSCC. Some clinical phase I/II studies about the combination with CDDP and S-1 have been reported. The combination showed a good response rate of 67.6% for advanced and recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined with carboplatin or nedaplatin have also been reported. Regimens containing S-1 appear to have been effective for HNSCC. Multi-institutional phase II studies with a large sample size are needed in the future. The compliance for patients is better than a 5-FU injection because S-1 is orally administrated. The adverse effect, especially for bone mallow toxicity, is equal or upgraded compared with a 5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia

S-1 is a newly developed oral anti-tumor agent, which contains 5-chloro-2, 4-dihydroxypyridine and potassium oxonate to strengthen biological activities of 5-fluorouracil. Response rate of S-1 for advanced non-small cell lung cancer was reported to be 12.5-22%. Response rate of combination chemotherapy with S-1 plus cisplatin (CDDP) was reported to be 47%, and the median survival time was 11 months. Adverse events of the combination chemotherapy were milder than other combination chemotherapy described before. Therefore, S-1 plus CDDP combination chemotherapy is a future candidate for phase III clinical study.

Topics: Administration, Oral; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Remission Induction; Tegafur

Cytotoxic agents such as anthracycline or taxanes have provided a good clinical response for breast cancer patients, although they have failed to prolong the survival rate and to improve the quality of life (QOL) of these patients. On the other hand, cytostatic agents such as 5-fluorouracil (5-FU) have to be focused to accommodate a long term progression with respect to efficacy and the patients' QOL improvement. S-1 was a newly developed and orally administered fluorinated pyrimidine containing 1 M tegafur (FT) and two classes of a modulator, 5-chloro-2,4-dihydroxypyrimidine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT : CDHP : Oxo= 1 : 0.4 : 1. Specific dose limiting factors such as neutropenia, diarrhea and stomatitis have been observed in a previous phase I study. Two phase II studies of 4 weeks treatment of S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) for the advanced or metastatic breast cancer patients were carried out in Japan. Among 108 evaluable patients for response, there were 10 complete response (CR) and 35 partial response (PR) with an overall response rate of 41.7% (95% confidence interval, 32.3-51.5%). The incidence of toxicity (> or = grade 3) was as followed: neutropenia 9.3%, anemia 0.9%, stomatitis 1.9% and nausea/vomiting 0.9%. The median follow-up period for patients was 802 days. S-1 will be the new promising oral agent like a capecitabine which has been widely used as a third-line chemotherapy for the heavily treated breast cancer patients.

Topics: Administration, Oral; Anemia; Antimetabolites, Antineoplastic; Breast Neoplasms; Carcinoma, Ductal, Breast; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Mastectomy, Segmental; Nausea; Neutropenia; Oxonic Acid; Quality of Life; Stomatitis; Survival Rate; Tegafur

This study aimed to evaluate the feasibility, safety, and efficacy of postoperative adjuvant chemotherapy with docetaxel/cisplatin/S-1 (DCS) following S-1 therapy in patients with stage III gastric cancer after curative gastrectomy.. Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Adjuvant chemotherapy was initiated within 8 weeks of gastrectomy. The first cycle of chemotherapy consisted of S-1 monotherapy (day 1-14), followed by a 7-day rest period. Cycles 2 and 3 consisted of the following: S-1 (day 1-14) administration, followed by a 14-day rest period, and an intravenous infusion of cisplatin and docetaxel on days 1 and 15. After two cycles, S-1 was administered for up to 1 year.. Thirty patients were enrolled between 2014 and 2017. Febrile neutropenia of grade 3 or higher was the most common hematological toxicity with 4 patients (13.3%). Other hematological toxicities of grade 3 or higher were as follows: neutropenia in 3 (10.0%), leukopenia in 3 (10.0%), and anemia in 2 (6.7%) patients. Most frequent non-hematological toxicity of grade 3 was anorexia (n = 4, 13.3%) and general fatigue (n = 3, 10.0%); no grade 4 non-hematological toxicities were observed. Twenty-five patients (83.3%) completed two cycles of DCS treatment and 18 (60.0%) completed subsequent S-1 treatment for 1 year. The relative dose intensity of docetaxel and cisplatin was 0.86 and that of S-1 was 0.88.. The DCS regimen can be acceptable as an adjuvant chemotherapy and offers an effective postoperative treatment option for stage III gastric cancer patients.. UMIN000012785 .. 08/01/2014.

Topics: Adenocarcinoma; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Fatigue; Feasibility Studies; Female; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Patient Compliance; Stomach Neoplasms; Tegafur

Combination carboplatin and S-1 is active in the treatment of non-small cell lung cancer (NSCLC). However, data on this combination for elderly patients with NSCLC are insufficient.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Survival Rate; Tegafur; Thrombocytopenia; Treatment Outcome

Neoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study.. Patients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148).. We enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (n = 101) and 74.6% in the on-protocol cohort (n = 44).. NAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm, Residual; Neutropenia; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prospective Studies; Survival Rate; Tegafur

The East Asia S-1 Trial in Lung Cancer (EAST-LC) was a randomized phase III study conducted in East Asia that demonstrated the non-inferiority of S-1 to docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). Here, we reported the results of the Japanese subgroup treated with docetaxel 60 mg/m. Patients were randomized 1:1 to receive either S-1 or docetaxel. The primary endpoint was overall survival (OS); the secondary endpoints included progression-free survival (PFS), response rate (RR), quality of life (QOL), and safety.. Patient characteristics in the Japanese subgroup (n = 724) were similar to those in the overall EAST-LC population. Median OS was 13.4 months in the S-1 group and 12.6 months in the docetaxel group. In pemetrexed-pretreated patients, OS with S-1 was similar to that with docetaxel. Median PFS was 2.9 and 3.0 months in the S-1 and docetaxel groups, respectively. RR was 9.4% and 10.3% in the S-1 and docetaxel groups, respectively. The QOL of patients treated with S-1 was better compared with that of patients treated with docetaxel. Decreased appetite and diarrhea were more common in the S-1 group, whereas the frequency of neutropenia and febrile neutropenia was markedly higher in the docetaxel group.. This Japanese subgroup analysis showed that S-1 had similar efficacy to docetaxel in patients with previously treated advanced NSCLC. These results are similar to those of the overall EAST-LC population.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Quality of Life; Tegafur; Treatment Outcome

Previous studies have shown sex-related differences in the incidence of adverse events following treatment with fluoropyrimidines, however the mechanism of this difference is unknown. We examined sex-related differences in the safety of S-1 plus oxaliplatin (SOX) and S-1 plus cisplatin (CS) in 663 metastatic gastric cancer patients taking part in a phase III study. The incidences of leukopenia (odds ratio [OR] 1.9; P = .015), neutropenia (OR 2.2; P = .002), nausea (OR 2.0; P = .009), and vomiting (OR 2.8; P < .001) were increased in women versus men treated with SOX, while vomiting (OR 2.9; P < .001) and stomatitis (OR 1.8; P = .043) were increased in women versus men treated with CS. In contrast, male patients treated with CS experienced thrombocytopenia more often (OR 0.51; P = .009). The mean relative dose intensity of S-1 in SOX was 75.4% in women and 81.4% in men (P = .032). No difference in efficacy was observed between women and men undergoing either regimen. Sex-related differences in adverse reactions during SOX and CS treatment were confirmed in this phase III study. Further translational research studies are warranted to pursue the cause of this difference.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Incidence; Male; Middle Aged; Nausea; Neutropenia; Oxaliplatin; Oxonic Acid; Sex Factors; Stomach Neoplasms; Stomatitis; Tegafur; Thrombocytopenia; Vomiting

This study compared the efficiency and safety of definitive concurrent chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus Cisplatin (CS) in unresectable locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients were retrospectively reviewed. We performed a propensity score matching analysis; 41 patients treated with the CS regimen were matched 1:1 to patients who received the TP regimen. Patient- and disease-related characteristics were well-balanced between the two groups. The CS group showed significantly better treatment compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49 days, P = 0.025) over the TP group during the CCRT course. The complete response rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1- and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4% compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and 3-year progression-free survival (PFS) rates in the TP group were 51.2% and 24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The incidence of severe and total neutropenia in the TP group was significantly higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate analysis revealed that T stage and the complete response rate were strong prognostic factors associated with OS and PFS. In conclusion, both treatment regimens yielded satisfactory survival outcomes, but the CS regimen could significantly improve treatment compliance, reduce hematological toxicities and lengths of hospital stay. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Drug Combinations; Esophageal Neoplasms; Female; Fluorouracil; Humans; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Paclitaxel; Remission Induction; Retrospective Studies; Tegafur; Vomiting

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Drugs, Chinese Herbal; Esophageal Neoplasms; Female; Humans; Karnofsky Performance Status; Leukopenia; Male; Nausea; Neutropenia; Oxonic Acid; Tegafur; Vomiting

A phase II study of S-1 plus leucovorin (LV) given in a 4-week schedule (2 weeks' administration followed by 2 weeks' rest) for patients with untreated metastatic colorectal cancer (mCRC) showed that the combination was effective, but grade 3 toxicities (diarrhea, stomatitis and anorexia) occurred at a relatively high rate. In this phase II study, we evaluated the efficacy and safety of a 2-week schedule of S-1 plus LV. Patients with mCRC received oral S-1 (40-60 mg) and LV (25 mg) twice daily for 1 week, followed by 1 week's rest. Treatment was repeated until disease progression or unacceptable toxicity. The primary endpoint was response rate. The pharmacokinetics of S-1 and LV in Chinese patients were evaluated on day 1 of the first cycle. Seventy-three patients were enrolled in Japan and China. Of 71 eligible patients, the response rate was 53.5%, and the disease control rate was 83.1%. Median progression-free survival and median overall survival were 6.5 and 24.3 months, respectively. The incidences of grade 3 toxicities were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8% and neutropenia 9.7%. There were no treatment-related deaths. The pharmacokinetics profiles of S-1 plus LV in Chinese patients were similar to those in Japanese patients. This 2-week schedule of S-1 plus LV showed good efficacy and better tolerability than the 4-week schedule. This therapy will be the base regimen for mCRC to be added by other cytotoxic or molecular-targeted drugs. The optimized treatment schedule for S-1 plus LV was 1 week on and 1 week off.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; China; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Japan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Stomatitis; Survival Analysis; Tegafur; Treatment Outcome

Gemcitabine (GEM) plus cisplatin (CDDP) chemotherapy has been used worldwide as the standard first-line treatment for advanced biliary tract cancer (BTC). A phase II trial has also suggested promising activity of GEM plus S-1 chemotherapy against advanced BTC. The aim of this study was to evaluate the efficacy and safety of GEM plus S-1 chemotherapy in patients with advanced BTC.. A total of 38 patients were enrolled between August 2008 and November 2011. There were 19 men and 19 women, with a median age of 66 years (range=44-81 years). Seven patients had a previous history of first-line or adjuvant chemotherapy after surgery. The PS was 0 and 1 in 30 and 7 patients, respectively. The treatment response was classified as partial response in 6 patients (15.8%) and as stable disease in 18 patients (47.4%). The median PFS and OS were 5.8 and 15.9 months, respectively. The toxicity was generally mild, and the most common grade 3/4 toxicities were leukopenia (31.6%), neutropenia (36.8%), nausea/vomiting (2.6%), and diarrhea (2.6%). There was one treatment-related death due to interstitial pneumonia.. Our study revealed that gemcitabine plus S-1 chemotherapy was well-tolerated and exhibited favorable antitumor activity in patients with advanced BTC.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Deoxycytidine; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome; Vomiting

S-1, a novel oral fluoropyrimidine, is active in the treatment of non-small cell lung cancer (NSCLC). However, data on S-1 for elderly patients with NSCLC are insufficient.. Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >70 years, and adequate hematological, hepatic, and renal functions. Patients received S-1 (40 mg/m(2) twice a day) for 28 consecutive days. This schedule was repeated every 6 weeks. The primary end point was the tumor response rate.. Thirty-two patients were enrolled and 31 patients were evaluable for response. The patients' median age was 80 years (range: 71-88). The response rate was 22.6% (95% CI: 11-38). Neutropenia, anemia, thrombocytopenia, febrile neutropenia, and diarrhea of grade ≥ 3 occurred in 6, 6, 10, 3, and 3%, respectively.. In elderly patients with previously untreated advanced NSCLC, S-1 appears to be well tolerated and demonstrates encouraging activity.

Topics: Aged; Aged, 80 and over; Anemia; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Nausea; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome; Vomiting

Oral fluoropyrimidines are used for the first-line treatment of metastatic breast cancer to avoid severe adverse effects, although firm supporting evidence is lacking. We aimed to establish whether S-1 is non-inferior to taxanes in this setting.. We did an open-label, non-inferiority, phase 3 trial at 154 hospitals in Japan. We enrolled individuals who had HER2-negative metastatic breast cancer who had received no chemotherapy for advanced disease, and who were resistant to endocrine treatment. Patients were randomly assigned (1:1) either to taxane (docetaxel 60-75 mg/m(2) at intervals of 3-4 weeks; paclitaxel 80-100 mg/m(2) weekly for 3 of 4 weeks; or paclitaxel 175 mg/m(2) at intervals of 3-4 weeks) or to S-1 (40-60 mg twice daily for 28 consecutive days, followed by a 14-day break). Randomisation was done centrally with the minimisation method, with stratification by institution, liver metastasis, oestrogen and progesterone receptor status, previous treatment with taxanes or oral fluorouracil, and time from surgery to recurrence. The primary endpoint was overall survival, with a prespecified non-inferiority margin of 1·333 for the hazard ratio (HR). The primary efficacy analysis was done in the full analysis set, which consisted of all patients who took at least one study treatment and who had all data after randomisation. This trial is registered with the University Hospital Medical Information Network, Japan (protocol ID C000000416).. Between Oct 27, 2006, and July 30, 2010, we enrolled 618 patients (309 assigned to taxane; 309 assigned to S-1). The full analysis set consisted of 286 patients in the taxane group and 306 in the S-1 group. Median follow-up was 34·6 months (IQR 17·9-44·4). Median overall survival was 35·0 months (95% CI 31·1-39·0) in the S-1 group and 37·2 months (33·0-40·1) in the taxane group (HR 1·05 [95% CI 0·86-1·27]; pnon-inferiority=0·015). The most common grade 3 or worse adverse events were neutropenia (20 [7%] of 307 patients in the S-1 group vs nine [3%] of 290 patients in the taxane group), fatigue (ten [3%] vs 12 [4%]), and oedema (one [<1%] vs 12 [4%]). Treatment-related deaths were reported in two patients in the taxane group.. S-1 is non-inferior to taxane with respect to overall survival as a first-line treatment for metastatic breast cancer. S-1 should be considered a new option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer.. Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan; Taiho.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Disease Progression; Disease-Free Survival; Docetaxel; Drug Combinations; Edema; Fatigue; Female; Follow-Up Studies; Health Status; Humans; Liver Neoplasms; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Rate; Taxoids; Tegafur

Although leucovorin enhances the efficacy of fluorouracil, the anti-tumour activity of S-1 and leucovorin and their combination with oxaliplatin for patients with advanced gastric cancer is unknown. We compared the activity and safety of S-1 plus leucovorin, S-1 plus leucovorin and oxaliplatin, and S-1 plus cisplatin as first-line chemotherapy for advanced gastric cancer.. In this multicentre, randomised, open-label, phase 2 trial, we recruited chemotherapy-naive patients with unresectable or recurrent gastric cancer with measurable lesions aged 20 years or older from 25 general hospitals and specialist centres in Japan. Patients were randomly assigned (1:1:1) centrally to receive S-1 plus leucovorin (S-1 40-60 mg orally plus oral leucovorin 25 mg twice a day for 1 week, every 2 weeks), S-1 plus leucovorin and oxaliplatin (S-1 plus leucovorin and intravenous oxaliplatin 85 mg/m(2) on day 1, every 2 weeks), or S-1 plus cisplatin (S-1 40-60 mg orally twice a day for 3 weeks, plus intravenous cisplatin 60 mg/m(2) on day 8, every 5 weeks). Randomisation was done with the minimisation method using performance status (0 vs 1) and tumour stage (stage IV vs recurrent) as stratification factors. The primary endpoint was independently reviewed overall response in the full analysis set. This trial is registered with Japic CTI, number 111635.. Between Oct 20, 2011, and Dec 17, 2012, we enrolled and randomly assigned 145 patients: 49 patients were assigned to S-1 plus leucovorin, 47 to S-1 plus leucovorin and oxaliplatin, and 49 to S-1 plus cisplatin. An objective response assessed by the independent review committee was achieved in 20 (43% [95% CI 28·3-57·8]) of the 47 patients in the S-1 plus leucovorin group, 31 (66% [50·7-79·1]) of the 47 patients in the S-1 plus leucovorin and oxaliplatin group, and 22 (46% [31·4-60·8]) of the 48 patients in the S-1 plus cisplatin group (Fisher's exact test, p=0·84 for S-1 plus leucovorin vs S-1 plus cisplatin, p=0·063 for S-1 plus leucovorin and oxaliplatin vs S-1 plus cisplatin, and p=0·038 for S-1 plus leucovorin and oxaliplatin vs S-1 plus leucovorin). The most common grade 3-4 adverse events were neutropenia (three [6%] of 48 patients in the S-1 plus leucovorin group vs 12 [26%] of 47 patients in the S-1 plus leucovorin and oxaliplatin group vs 17 [35%] of 49 patients in the S-1 plus cisplatin group), decreased appetite (six [13%] vs 14 [30%] vs 12 [24%]), anaemia (five [10%] vs seven [15%] vs 13 [27%]), and hyponatraemia (two [4%] vs two [4%] vs nine [18%]).. S-1 plus leucovorin and oxaliplatin was more active than S-1 plus leucovorin or S-1 plus cisplatin with acceptable toxic effects for patients with advanced gastric cancer. A phase 3 trial comparing S-1 plus leucovorin and oxaliplatin with S-1 plus cisplatin is underway.. Taiho Pharmaceutical.

Topics: Adenocarcinoma; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Feeding and Eating Disorders; Female; Humans; Hyponatremia; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

Combination chemotherapy with S-1 and irinotecan is one of the standard treatments for metastatic colorectal cancer (mCRC) in Japan. However, there are few alternative practical second-line therapies. We conducted a phase II trial to evaluate the efficacy and safety of the combination of S-1 and irinotecan plus bevacizumab as a second-line treatment for oxaliplatin-refractory mCRC.. Patients with mCRC who were previously treated with oxaliplatin-containing regimens were enrolled. Oral S-1 at a dose of 40 mg/m(2) was administered twice daily for 2 weeks, followed by a 1-week drug-free interval. Irinotecan at a dose of 150 mg/m(2) and bevacizumab at a dose of 7.5 mg/kg were administered on day 1. The primary endpoint was progression-free survival (PFS).. Thirty-seven patients were enrolled, and 34 and 36 patients were assessed for response and safety, respectively. The overall response rate was 20.6 % (95 % confidence interval [CI] 8.7-37.9), and the disease control rate was 76.5 % (95 % CI 58.8-89.3). The median PFS was 5.6 months (95 % CI 3.8-7.0). The median overall survival was 16.4 months (95 % CI 8.1-20.0). The most common grade 3/4 adverse events included neutropenia (25.0 %), anorexia (22.2 %), anemia (16.7 %), and fatigue/malaise (16.7 %). The most common grade 3/4 adverse event of special interest for bevacizumab was hypertension (30.6 %). One treatment-related death caused by gastrointestinal bleeding occurred.. The findings suggest that the combination of S-1 and irinotecan plus bevacizumab is effective and tolerable as second-line chemotherapy for patients with oxaliplatin-refractory mCRC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Irinotecan; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur; Treatment Outcome

Although standard chemotherapy for esophageal cancer patients is fluorouracil and cisplatin, the prognosis is still unsatisfactory. A new therapeutic regimen combining docetaxel, cisplatin, and 5-fluorouracil was recently developed to improve both local and distant tumor control. We developed a new regimen of docetaxel, nedaplatin, and S1 (DGS) and previously reported the recommended dose in a phase I dose-escalation study. We then undertook a phase II study of DGS for advanced esophageal squamous cell carcinoma. Patients with clinical stage IB/II/III disease were eligible. Patients received two courses of chemotherapy: docetaxel 35 mg/m(2) with nedaplatin 40 mg/m(2) on day 8, 80 mg/m(2) S1 on days 1-14, and 2 weeks off. After completion of chemotherapy, patients underwent esophagectomy. The primary endpoint was the completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery [no residual tumor]). We enrolled 32 patients. The completion rate of protocol treatment was 96.9%. During chemotherapy, the most common grade 3 or 4 toxicity was neutropenia (25.0%). No treatment-related deaths were observed, and the incidence of operative morbidity was tolerable. The overall response rate after chemotherapy was 83.3%. This DGS regimen was well tolerated and highly active. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014626).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Taxoids; Tegafur; Treatment Outcome

The purpose of this phase I study of the dose escalation of oxaliplatin in combination with oral S-1 and pelvic radiation preoperatively for poor-risk lower rectal cancer was to determine the dose-limiting toxicity (DLT) and recommended dose of oxaliplatin.. Patients with cT4 and lateral pelvic lymph node metastasis, and without distant metastasis (cM0), were treated with weekly oxaliplatin, oral S-1 40 mg/m(2) twice daily for 5 days a week, and radiation. A total of 5 weekly doses of oxaliplatin were planned. RT was administered to a total dose of 50.4 Gy in 28 fractions.. We enrolled 11 patients between December 2009 and January 2012. DLTs were observed at dose level 1 (50 mg/m(2)) in two patients, one of whom experienced grade 3 aspartate aminotransferase elevation and a grade 3 alanine aminotransferase increase, and the other developed grade 4 hypokalemia and a grade 3 alanine aminotransferase increase. Five patients at dose level 2 (60 mg/m(2)) showed no DLTs. The hematological toxicities in all patients were mild and reversible. One patient showed distant metastasis after chemoradiation. Ten of the 11 patients achieved R0 resection by mesorectal resection and lateral lymph node dissection; three of the 10 underwent combined resection of the other organs.. This phase I trial of preoperative S-1 in combination with oxaliplatin and radiation for lower rectal cancer with T4 and lateral pelvic lymph node metastasis revealed that the recommended dose of oxaliplatin was 60 mg/m(2) weekly.

Topics: Adenocarcinoma; Adult; Aged; Alanine Transaminase; Antineoplastic Combined Chemotherapy Protocols; Aspartate Aminotransferases; Chemoradiotherapy, Adjuvant; Diarrhea; Dose Fractionation, Radiation; Drug Combinations; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pelvis; Preoperative Care; Rectal Neoplasms; Tegafur; Vomiting

S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective phase 1 trial to determine the maximum tolerated dose (MTD) of S-1 and rates of dose-limiting toxicities (DLTs) associated with HAI of gemcitabine in patients with unresectable BTC.. BTC patients were treated with 21-day cycles of HAI of gemcitabine (1000 mg/m(2) on days 1 and 8) and oral S-1 (60, 70, or 80 mg/m(2) on days 1-14) until disease progression occurred.. Fifteen patients were enrolled in the study. Grade 3 and 4 neutropenia occurred in five of 15 (33%) patients. Among six patients who were treated with 60 mg/m(2) S-1, one developed grade 4 neutropenia. DLTs (grade 4 neutropenia and bladder infection) occurred in two of six patients who were treated with 70 mg/m(2) S-1. Two of the three patients who were treated with 80 mg/m(2) S-1 experienced DLTs (grade 4 leukopenia and neutropenia and grade 3 febrile neutropenia). Thus, 80 mg/m(2) was defined as the MTD of S-1.. The MTD of oral S-1 in GS therapy is 80 mg/m(2). Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Hepatic Artery; Humans; Infusions, Intra-Arterial; Male; Maximum Tolerated Dose; Middle Aged; Neutropenia; Oxonic Acid; Tegafur

To determine the recommended dose (RD) for full-dose S-1 and low-dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer.. Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days).. Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%).. The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Radiation Pneumonitis; Tegafur; Treatment Outcome

Locally advanced gastric cancer with extensive regional and/or para-aortic lymph node (PAN) metastases is typically unresectable and associated with poor outcomes. This study investigated the safety and efficacy of S-1 plus cisplatin followed by extended surgery with PAN dissection for gastric cancer with extensive lymph node metastasis.. Patients with gastric cancer with bulky lymph node metastasis along the coeliac artery and its branches and/or PAN metastasis received two or three 28-day cycles of S-1 plus cisplatin, followed by gastrectomy with D2 plus PAN dissection. The primary endpoint was the percentage of complete resections with clear margins in the primary tumour (R0 resection). A target sample size of 50 with one-sided α of 0.105 and β of approximately 0.2 corresponded to an expected R0 rate of 65 per cent and a threshold of 50 per cent.. Between February 2005 and June 2007, 53 patients were enrolled, of whom 51 were eligible. The R0 resection rate was 82 per cent. Clinical and pathological response rates were 65 and 51 per cent respectively. The 3- and 5-year overall survival rates were 59 and 53 per cent respectively. During chemotherapy, grade 3/4 neutropenia occurred in 19 per cent and grade 3/4 non-haematological adverse events in 15.4 per cent. The incidence of grade 3/4 adverse events related to surgery was 12 per cent. There were no reoperations or treatment-related deaths.. For locally advanced gastric cancer with extensive lymph node metastasis, 4-weekly S-1 plus cisplatin followed by surgery including PAN dissection was safe and effective for some patients. Further investigation of this treatment strategy is warranted.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Postoperative Complications; Stomach Neoplasms; Tegafur; Treatment Outcome

The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1.. We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20-80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0-1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m(2) per day), S-1 only (80 mg/m(2) per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m(2)) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082.. We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2-57·6) and that of sequential treatment was 57·2% (53·4-60·8; hazard ratio [HR] 0·92, 95% CI 0·80-1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2-56·6) and that of the S-1 group was 58·2% (54·4-61·8; HR 0·81, 95% CI 0·70-0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3-4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3-4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively).. Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan.. Epidemiological and Clinical Research Information Network.

Topics: Adenocarcinoma; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Uracil

Second-line chemotherapy is now considered a standard therapy option in patients with advanced gastric cancer (AGC) who failed from first-line chemotherapy. Single agents, such as irinotecan, docetaxel or paclitaxel, provided an overall response rate of about 10 %. However, the efficacy was not satisfactory. The authors conducted a phase II study to investigate biweekly regimen of S-1 plus paclitaxel in Chinese AGC in second-line setting, with response rate as the primary end point.. Patients with AGC failed from first-line chemotherapy with fluoropyrimidine/platinum who had measurable lesions were enrolled. Paclitaxel was administered intravenously on day 1 at a dose of 120 mg/m(2), and oral S-1 was administered twice a day from days 1 to 7, followed by a 7-day drug-free interval.. A total of 30 patients with pretreated AGC were accrued. No complete responses were observed. Partial responses were documented in 10 (33.3 %) patients. Ten (33.3 %) patients had stable disease. The median progression-free survival was 3.6 months and the overall survival was 7.2 months. The main toxicity was bone marrow suppression. The most frequent grade 3/4 hematological toxicities were neutropenia and anemia, which were observed in 8 (26.7 %) and 6 (20 %) patients, respectively. The most common grade 3/4 non-hematological toxicity was neuropathy, which was reported in 4 (13.3 %) patients.. Biweekly S-1 plus paclitaxel showed promising activity with acceptable toxicities as second-line chemotherapy in pretreated patients with AGC. This regimen deserves further investigation in a phase III trial.

Topics: Administration, Oral; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Asian People; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Injections, Intravenous; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Platinum; Stomach Neoplasms; Tegafur; Treatment Outcome

A phase II study was performed to investigate the safety and efficacy of concurrent chemoradiotherapy (CCRT) combined with an orally active fluoropyrimidine, S-1, plus cisplatin for locally advanced esophageal cancer (LAEC).. CCRT comprised 2 courses, a 30-Gy radiotherapy over 3 weeks plus daily oral S-1 (80 mg/m(2)/day) for 2 weeks and a 24-hour cisplatin infusion (70 mg/m(2)) on day 8, and an identical course administered after a 2-week break.. One hundred and sixteen patients, 12 with stage II, 71 with stage III, and 33 with stage IVa LAEC participated, and 106 of them (91.4%) completed the CCRT course. The most serious toxicity was myelosuppression: grade 3 and 4 neutropenia occurred in 28.4 and 9.5% of patients, respectively. Nonhematologic toxicity was moderate. Complete response rates in patients with stage II, III, and IVa LAEC were 91.7, 67.6, and 36.4%, respectively. The overall median survival time was 2.3 years and that of patients with stage II, III, and IVa cancer was 7.0, 2.6, and 1.3 years, respectively.. CCRT combined with S-1 plus cisplatin showed promising safety and efficacy. Potentially, this combination therapy could become a baseline medication for patients with LAEC.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Disease Progression; Drug Combinations; Esophageal Neoplasms; Female; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Radiotherapy Dosage; Survival Rate; Tegafur; Thrombocytopenia; Time Factors; Treatment Failure

We conducted a phase I study of S-1 combined with irinotecan and oxaliplatin (TIROX) to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety, pharmacokinetics, pharmacogenetics, and preliminary efficacy in patients with metastatic colorectal cancer (MCRC) or metastatic gastric cancer (MGC).. Patients received escalating doses of S-1 (30-40 mg/m² b.i.d.) orally on days 1-14, an escalating dose of intravenous irinotecan (120-150 mg/m²) on day 1, and a fixed dose of intravenous oxaliplatin (85 mg/m²) on day 1 every 3 weeks.. Twenty-three patients (10 MCRC, 13 MGC; 13 chemonaive, 10 previously treated for metastatic disease) were treated across six dose levels. Because only one patient experienced a dose-limiting toxicity of grade 3 anorexia at the highest dose level (S-1 40 mg/m² b.i.d., irinotecan 150 mg/m², and oxaliplatin 85 mg/m²) (n = 8), the MTD was not obtained, and this level was established as the RD. With a median of 10 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (43 %), diarrhea (13 %), and nausea (13 %). In 22 efficacy-evaluable patients, the objective tumor response rate was 59.1 % (75 % for both MCRC and MGC in the first-line setting) and the disease control rate was 100 %. The exploratory pharmacokinetic/pharmacogenetic study showed that CYP2A6 variants (*4, *7, *9) are associated with a lower metabolic ratio of S-1 (exposure ratio of 5-fluorouracil to tegafur).. The new triplet TIROX regimen has shown promising antitumor activity and a favorable toxicity profile in patients with MCRC and MGC.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Camptothecin; Cohort Studies; Colorectal Neoplasms; Cytochrome P-450 CYP2A6; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Half-Life; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Survival Analysis; Tegafur

To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC).. S-1 (50mg/m(2)) was administered orally twice daily for 14 days, with cisplatin (40 mg/m(2)) on days 1 and 8 of each cycle every 3 weeks, for 2-4 cycles. Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy. The primary endpoint was the response rate, and secondary endpoints included progression-free survival, overall survival and safety.. Forty-one patients were enrolled in this study. The objective response rate was 87.8% (98% CI: 77.8-97.8%). The median progression-free survival was 467 days (15.4 months), and the median survival time was 904 days (29.7 months). The overall survival rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%). No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in one patient.. The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC.

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur

We previously reported on the regimen of S-1 plus nedaplatin (NDP), with S-1 was administered orally for 14 days and NDP intravenously on day 8. The maximum tolerated dose (MTD) of NDP was determined to be 90 mg/m². The main toxicities were neutropenia and thrombocytopenia. This result was tolerated, but we believe there is a more effective and tolerable regimen. Thus, we investigated the S-1 regimen administered orally for 14 days, and NDP intravenously on day 1 in patients with locally advanced head and neck squamous cell carcinoma.. Oral administration of S-1 (days 1-14) and intravenous NDP (day 1) were tested for patients with advance head and neck cancer in a phase I setting. The dose of S-1 was fixed and the dose of NDP was escalated from 70 mg/m², with an increase of 10 mg/m² per step, to find the MTD.. A total of 15 patients were registered. The MTD of NDP was determined to be 100 mg/m². The main toxicities were neutropenia and thrombocytopenia. The response rate (RR) was 57.1%.. The recommended dose of NDP for a phase II study was determined to be 100 mg/m². We concluded that our regimen was well tolerated and that the RR was acceptable.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Tegafur; Thrombocytopenia; Treatment Outcome

S-1 and cisplatin combination therapy is a standard regimen for patients with advanced gastric cancer in Japan. The primary objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of a triplet regimen adding paclitaxel to S-1 and cisplatin combination therapy.. Patients with previously untreated metastatic or recurrent gastric cancer were enrolled. Patients received S-1 (40 mg/m(2) p.o., twice daily, on days 1-21 every 35 days), cisplatin (30 mg/m(2) divided, on days 1 and 15) and paclitaxel (divided on days 1 and 15). The starting dose of paclitaxel was 50 mg/m(2) (level 1); the dose was escalated to 60 (level 2), 70 (level 3) and 80 mg/m(2) (level 4) in a stepwise fashion. Dose-limiting toxicity was determined during the first treatment cycle.. Eighteen patients enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, one of the six patients had dose-limiting toxicity (one patient had grade 4 neutropenia) and at dose level 4, one of the six patients had dose-limiting toxicity (one patient had febrile neutropenia, hypoalbuminemia and fatigue of grade 3). The maximum tolerated dose was not reached at level 4; however, grade 3 hyponatremia and hypokalemia in two of the six patients occurred during the second treatment course at level 4. From the point of view of safety in the outpatient setting, the recommended dose of paclitaxel was determined at 70 mg/m(2). The overall response rate was 50%.. The recommended dose of paclitaxel added to S-1 (80 mg/m(2) days 1-21) plus cisplatin (30 mg/m(2) days 1 and 15) was 70 mg/m(2) on days 1 and 15 of a 5-week cycle.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Fatigue; Female; Humans; Hypoalbuminemia; Hypokalemia; Hyponatremia; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

In Japan, a study comparing the effectiveness and safety of irinotecan plus S-1 (IRIS) with those of a combination of 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line treatment in patients with advanced or recurrent colorectal cancer demonstrated that IRIS was non-inferior to FOLFIRI. We previously reported that IRIS is also effective as first-line treatment.. Eligibility criteria included inoperable recurrent colorectal cancer with a confirmed diagnosis of adenocarcinoma, age ≥20 years, and no history of prior chemotherapy. S-1 (40-60 mg twice daily) was given orally on Days 1 to 14, and irinotecan (100 mg/m(2)) and bevacizumab (5 mg/kg) were given intravenously on Days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS).. A total of 52 eligible patients were enrolled from October 2007 through March 2009. In safety analysis, the incidences of grade 3 or 4 adverse reactions were as follows: neutropenia, 27%; hypertension, 21%; and diarrhea, 17%. The overall response rate was 57.7%. Median progression-free survival was 16.7 months.. IRIS plus bevacizumab is a well-tolerated, highly effective chemotherapeutic regimen that is easy to administer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Hypertension; Irinotecan; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Severity of Illness Index; Tegafur; Treatment Outcome

We evaluated the efficacy and safety of a combination of S-1 and cisplatin (SP) versus gemcitabine and cisplatin (GP) as first-line therapy for advanced biliary tract adenocarcinoma (ABTA).. Patients were randomized to receive cisplatin (60 mg/m(2) intravenously [IV] on Day 1) plus S-1 (40 mg/m(2) bid orally on Days 1-14) or gemcitabine (1000 mg/m(2) IV at 10 mg/m(2)/min on Days 1 and 8) every three weeks. The primary end point was six-month progression-free survival (PFS).. Of 96 eligible patients, 49 were randomized to GP and 47 to SP. At a median follow-up time of 14.2 months, the six-month PFS rates were 43.8% and 34.7%, respectively [unadjusted HR (GP/SP) =0.85, 95% CI 0.52-1.36]. The median OS values in the GP and SP groups were 10.1 months and 9.9 months, respectively [unadjusted HR (GP/SP) =0.72, 95% CI 0.45-1.17]. Grade 3-4 toxicities in the GP and SP groups included neutropenia (49.0% vs. 31.8%), anemia (22.4% vs. 2.3%), thrombocytopenia (22.4% vs. 4.5%), and asthenia (4.1% vs. 2.1%).. Both GP and SP has comparable efficacy with favorable safety profile as first-line treatment for ABTA. (ClinicalTrials.gov number NCT 01375972).

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Biliary Tract Neoplasms; Cisplatin; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Severity of Illness Index; Tegafur; Thrombocytopenia; Treatment Outcome

To establish a safe, long-term regimen of docetaxel (DOC) and cisplatin (CDDP) in an outpatient setting for gastric cancer refractory to S-1 adjuvant chemotherapy, a dose-escalating phase I study was conducted. Cohorts of patients were treated with escalating doses of DOC (starting at 20 mg/m² per week with 5 mg/m² increments) and a fixed dose of CDDP (25 mg/m²). Drugs were administered on days 1, 8, and 15. A cycle of this treatment was 28 days. In total, 52 courses were performed, and the mean number of courses was 5.3. Two of the four patients at dose level 3 showed dose-limiting toxicities (grade 4 neutropenia, and grade 3 anorexia and dehydration). The recommended dose (RD) of DOC was therefore defined as 25 mg/m². There is a need for a phase II clinical trial using this regimen in patients with S-1-refractory stage II/III gastric cancer.

Topics: Aged; Anorexia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Cohort Studies; Dehydration; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose.. Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m2/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m2/day, gradually increasing to 60, 70, and 80 mg/m2/day. Surgery was performed within 6±2 weeks.. Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m2/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%).. The recommended dose of S-1 was determined to be 80 mg/m2/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Thrombocytopenia; Vomiting

We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting.. Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8 Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80 mg/m2 on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80 mg/m2) was infused on Days 1, 8, 22, and 29. Four or more weeks after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety.. We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea.. A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Diarrhea; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Irinotecan; Japan; Leukopenia; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neutropenia; Oxonic Acid; Rectal Neoplasms; Tegafur

This phase II trial first describes the combination chemotherapy of biweekly irinotecan plus S-1 (biweekly IRIS) for pretreated advanced gastric cancer (AGC) patients.. Patients who had previously been treated with greater than or equal to one regimen were enrolled. They received S-1 35 mg/m(2) twice daily on days 1-14 and irinotecan 150 mg/m(2) on days 1 and 15, every 4 weeks. The primary endpoint was overall survival (OS).. Among the 38 patients enrolled, 18 patients were treated as second line, and the remaining 20 patients were enrolled as third- or fourth line. A total of 208 cycles were administered with the median being four cycles (range 1-16). The median OS was 8.7 months [95% confidence interval (CI) 7.5-10.3], and the median progression-free survival was 6.3 months (95% CI 5.3-7.3). Low serum albumin (<3.5 mg/dL) was an independent adverse prognosticator for survival. Overall response rate was 17% (95% CI 4-30%). The major grade 3/4 toxicities were neutropenia (26%) and diarrhea (18%).. Biweekly IRIS showed the moderate activity as salvage treatment in AGC. Considering high neutropenia and gastrointestinal toxicity, patient selection should be warranted; serum albumin may be a predictive factor for treatment decision.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Diarrhea; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neutropenia; Oxonic Acid; Patient Selection; Salvage Therapy; Serum Albumin; Stomach Neoplasms; Survival; Tegafur; Treatment Outcome

This phase II study was designed to evaluate the efficacy and safety of oral fluoropyrimidine S-1 plus irinotecan (IRIS regimen) in patients with previously untreated metastatic colorectal cancer.. The response rate was the primary endpoint. Safety, progression-free survival time, and median survival time were secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer. Irinotecan was administered at a dose of 100 mg/m² (on days 1 and 15). S-1 (40 mg/m²) was administered for 2 weeks (on days 1 to 14) and followed by a 2-week rest.. Forty patients were enrolled. Four patients had grade 4 neutropenia, and six patients had grade 3 diarrhea. No other serious hematologic or nonhematologic adverse reactions occurred, and all patients received IRIS safely on an outpatient basis. The response rate was 52.5% (95% confidence interval [CI], 36.1-68.5%). Median progression-free survival was 8.6 months (95% CI, 5.3-11.9), and median survival time was 23.4 months (95% CI, 15.9-30.8).. IRIS produced a high response rate and could be given safely. IRIS may become a first-line treatment for inoperable or recurrent advanced colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome

To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer.. A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m²) was administered by infusion for 3 h on the first day. S-1 (70 mg/m²/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m²) was administered intravenously over 24 h on day 14 of every 28-day cycle.. All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months.. Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia; Treatment Outcome

The aim of this multicenter Phase II study was to assess the efficacy and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic cancer.. Chemotherapy-naïve patients with histologically or cytologically proven metastatic pancreatic adenocarcinoma were eligible for this study. Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated every 3 weeks.. A total of 55 patients were included and the efficacy and toxicity were analyzed in 54 patients who received at least one dose of gemcitabine and S-1 combination therapy. Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44.4% (95% confidence interval: 30.9-58.6%). The median progression-free survival was 5.9 months (95% confidence interval: 4.1-6.9 months) and the median overall survival was 10.1 months (95% confidence interval: 8.5-10.8 months) with a 1-year survival rate of 33.0%. The major Grade 3-4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%). Hematological toxicity was mostly transient and there was only one episode of febrile neutropenia ≥Grade 3.. Gemcitabine and S-1 combination therapy produced a high response rate with good survival in patients with metastatic pancreatic cancer. A randomized Phase III study to confirm the efficacy of gemcitabine and S-1 combination therapy is ongoing.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Eruptions; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Thrombocytopenia; Treatment Outcome

To evaluate the combination chemotherapy using oral antimetabolite S-1 plus cisplatin (SP) with concurrent thoracic radiotherapy (RT) followed by the consolidation SP for locally advanced non-small cell lung cancer.. Patients with stage III non-small cell lung cancer, 20 to 74 years of age, and Eastern Cooperative Oncology Group performance status 0 to 1 were eligible. The concurrent phase consisted of full dose S-1 (orally at 40 mg/m/dose twice daily, on days 1-14) and cisplatin (60 mg/m on day 1) repeated every 4 weeks for two cycles with RT delivered beginning on day 1 (60 Gy/30 fractions over 6 weeks). After SP-RT, patients received an additional two cycles of SP as the consolidation phase.. Fifty-five patients were registered between November 2006 and December 2007. Of the 50 patients for efficacy analysis, the median age was 64 years; male/female 40/10; Eastern Cooperative Oncology Group performance status 0/1, 21/29; clinical stage IIIA/IIIB 18/32; and adenocarcinoma/others 20/30. There were 42 clinical responses including one complete response with an objective response rate of 84% (95% confidence interval [CI], 71-93%). The 1- and 2-year overall survival rates were 88% (95% CI, 75-94%) and 70% (95% CI, 55-81%), respectively. The median progression-free survival was 20 months. Of the 54 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 neutropenia (26%), thrombocytopenia (9%), and grade 3 esophagitis (9%) and febrile neutropenia (9%). In one patient, grade 3 pneumonitis was observed in the consolidation phase. There were two treatment-related deaths caused by infection in the concurrent phase.. SP-RT showed a promising efficacy against locally advanced NCSLC with acceptable toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Dose Fractionation, Radiation; Drug Combinations; Esophagitis; Female; Fever; Humans; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia; Treatment Outcome

We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced gastric cancer (AGC).. Oxaliplatin was fixed at a dose of 130 mg/m2 on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m2 per day from 70 mg/m2 per day up to 100 mg/m2 per day. Pharmacokinetic analyses were performed following a single dose of S-1 on D-5 and D1 of the first cycle.. In phase I (n=18), MTD was not defined. In phase II (n=47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0-9.2 months) and the median overall survival was 12.5 months (95% CI 9.2-15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle.. The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Metabolic Clearance Rate; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur; Thrombocytopenia; Treatment Outcome; Vomiting

To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer.. Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, with at least one measurable lesion were eligible for the study. Gemcitabine at a dose of 1,000 mg/m2 was intravenously given over 30 min on days 1 and 8, while S-1 at a dose of 40 mg/m2 was orally given twice daily from day 1 to 14, and the cycle was repeated every 3 weeks. The objective response rate, which was assessed according to RECIST criteria, was the primary end point.. A total of 38 patients were enrolled between June 2006 and June 2007. The median number of treatment courses was 5.5 (range 1-22). Thirty-four patients were evaluable for response. Although no complete response was seen, partial responses were achieved in 11 patients, resulting in an overall response rate of 32% [95% confidence interval (CI) 17-48%]. The median response duration was 6.0 months (95% CI 4.6-8.3 months), the median time-to-progression was 5.4 months (95% CI 2.9-8.0 months), and the median overall survival was 8.4 months (95% CI 5.7-11.1 months). The major grade 3/4 hematologic toxicities were neutropenia (39.5%), leukopenia (15.8%), thrombocytopenia (2.6%), and anemia (7.9%). The major grade 3/4 non-hematologic toxicities included anorexia (10.5%), stomatitis (2.6%), rash (7.9%), fatigue (7.9%) and hyperbilirubinemia (5.3%).. Gemcitabine and S-1 combination chemotherapy was effective and tolerable in patients with unresectable pancreatic cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Fatigue; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Treatment Outcome

We conducted a phase II study of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin AUC 5 on day 1 of each cycle, and this was repeated every 4 weeks. Twenty-nine patients were enrolled in this study. The main grade 3 or 4 toxicities observed during the first cycle were neutropenia (10.3%), thrombocytopenia (41%), and transaminase elevation. Objective responses were seen in 9 patients (response rate 31.0%). The median survival time and median progression-free survival were 16.0 months (95% CI, 12.1-19.0 months) and 4.5 months (95% CI, 3.2-6.1 months), respectively. Hematological adverse events reaching grade 3 or 4 were neutropenia (10.3%), anemia (3.4%), and thrombocytopenia (3.4%). No febrile neutropenia was detected. Nonhematological toxicities were also mild. Although grade 3 infection was observed in 1 patient, the patient improved without intervention. The combination of S-1 plus carboplatin is an active and well-tolerated regimen for the treatment of patients with advanced NSCLC. Further investigations are required to confirm our results in randomized trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia

To evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer.. Patients with a measurable lesion and no previous history of chemotherapy or radiotherapy were enrolled. Gemcitabine was administered intravenously at a dose of 1,000 mg/m(2) over 30 min on day 1 and 15, repeated every 4 weeks. S-1 was administered orally at a dose of 40 mg/m(2) b.i.d. on days 1-14. Tumor response was assessed every two cycles using Response Evaluation Criteria in Solid Tumors criteria.. As much as 35 patients were enrolled between December 2006 and July 2008; 14 patients (40%) with gallbladder cancer and 14 (40%) with intrahepatic cholangiocarcinoma were included and 7 patients (20%) had received previous surgical resection. The overall response rate was 34.3% and the overall disease control rate was 82.9%. The median overall survival time was 11.6 months (95% CI, 7.3-15.6 months), and the median time to progression was 5.9 months (95% CI, 4.0-7.7 months). The grade 3/4 toxicities were leucopenia (23%), neutropenia (34%), anemia (20%), thrombocytopenia (6%) and anorexia (3%).. Gemcitabine and S-1 combination chemotherapy has promising efficacy and good tolerability in patients with advanced biliary tract cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome

This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer.. Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25-60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses.. Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7-37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes.. The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

Topics: Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Drug Combinations; Fatigue; Female; Humans; Leukopenia; Male; Metabolic Clearance Rate; Neutropenia; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

The purpose of this phase I/II study is to evaluate a new combination chemotherapy consisting of docetaxel and S-1 as front-line therapy for patients with untreated advanced non-small cell lung cancer (NSCLC). The treatment included docetaxel on day 1 and oral S-1 at a fixed dose of 40mg/m(2) administered twice daily on days 1-14 and repeated every 3 weeks. In phase I, docetaxel at escalating doses of 40 (level 0), 50 (level 1) and 60mg/m(2) (level 2) was administered starting from level 1. Because only one patient among the 6-patient cohort at level 1 and no patient among the 3-patient cohort at level 2 experienced defined dose-limiting toxicity (DLT), level 2 was determined as the recommended dose. In phase II, 60 patients were treated at the recommended dose for median 3 cycles, and the overall response rate was 30% (95% confidence interval [CI], 18.9-43.2%), and the median overall and progression-free survival times were 15.2 (95% CI: 10.5-17.7) and 4.9 (95% CI: 3.5-5.6) months, respectively. The most frequent toxicities experienced were neutropenia, febrile neutropenia and appetite loss; all toxicities were however well manageable. The present regimen showed a potent activity with mild toxicity in untreated NSCLC.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Non-Small-Cell Lung; Disease Progression; Docetaxel; Drug Combinations; Drug Dosage Calculations; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Survival Analysis; Taxoids; Tegafur

We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer.. Patients with histologically proven, unresectable metastatic gastric adenocarcinoma, performance status (PS) 0-2, and no prior chemotherapy were eligible. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m(2)) and docetaxel (60 mg/m(2)) on day 8 every 3 weeks.. Thirty-four patients were enrolled between March 2005 and April 2007. Three patients were considered ineligible and did not receive the DSC therapy. Clinical characteristics were as follows: median age, 63 years (range, 44-77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well-differentiated/undifferentiated adenocarcinoma, 10/21. The objective response rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%) in 31 assessable patients. Four had stable disease (12.9%) but none had progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7 (22.6%) underwent curative surgery. The median survival time and progression-free survival were 687 days [confidence interval (95% CI), 600.0-1,138.1] and 226 days (95% CI, 182.5-379.3), respectively. Most common grade 3/4 hematologic toxicity was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved, and no toxic deaths were observed.. DCS combination chemotherapy is highly active against unresectable metastatic gastric cancer and can be given safely with proper management of adverse events. Further studies of this combination are warranted.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Granulocyte Colony-Stimulating Factor; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Treatment Outcome

The purpose of the present phase II study was to evaluate both the efficacy and toxicity of the combination of S-1 and docetaxel in previously treated patients with locally advanced or metastatic non-small cell lung cancer.. Thirty-eight previously treated patients with non-small cell lung cancer were treated with S-1 (80 mg/m(2), days 1-14, oral) and docetaxel (40 mg/m(2), day 1, intravenous) every 3 weeks.. No complete response was observed, and seven patients had a partial response, yielding an overall response rate of 18.4% (95% CI, 7.7-34.3%). The median overall survival time and 1-year overall survival rate were 16.1 months and 60%, respectively. The median progression-free survival time was 4.4 months. Myelosuppression was the main toxicity with grade 3 or 4 neutropenia and leukopenia in 50 and 21%, respectively. There was no irreversible toxicity in this study.. The combination of S-1 and docetaxel is well tolerable and has substantial activity for patients with locally advanced or metastatic non-small cell lung cancer. A phase III trial comparing docetaxel with or without S-1 would warrant further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Survival Rate; Taxoids; Tegafur; Treatment Outcome

A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events.. In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m(2), for a total daily dose of 80 mg/m(2). The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation.. Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2).. The use of S-1 at 80 mg/m(2) per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life.

Topics: Aged; Aged, 80 and over; Anemia; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Glottis; Humans; Kaplan-Meier Estimate; Laryngeal Neoplasms; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Radiotherapy; Tegafur; Treatment Outcome

S-1 is a fourth-generation oral fluoropyrimidine that was developed to mimic the effects achieved with protracted continuous infusion of 5-fluorouracil (5-FU). This phase II study evaluated the efficacy and safety of S-1 salvage chemotherapy in patients with paclitaxel- and cisplatin-refractory gastric cancer. The primary end point was progression-free survival; secondary end points were overall survival, safety, and clinical benefit.. Patients were eligible for the study if they had histologically documented gastric adenocarcinoma previously treated with paclitaxel and cisplatin, age > or = 18 years, Eastern Clinical Oncology Group performance status < or =2, adequate organ function, and no evidence of gastrointestinal obstruction or passage disturbance. Patients were treated with a dose of S-1 based on body surface area (BSA) as follows: BSA < 1.25 m(2), 80 mg/day; 1.25 < or = BSA < 1.5 m(2), 100 mg/day; BSA > or= 1.5 m(2), 120 mg/day. The total dose was divided in two and administered twice daily for 4 weeks followed by a 2-week rest period.. Of the 53 patients enrolled in this study, 49 were evaluable. A total of 190 chemotherapy cycles were administered, and the median number of cycles was 2. Five patients (9.4%) had a partial response, and 18 (34%) had stable disease. Median progression-free survival and overall survival were 4.9 and 10.4 months, respectively. Grade 3/4 hematological toxicities included neutropenia in six patients (11%) but no cases of febrile neutropenia were found. Most of the non-hematological toxicities were diarrhea, asthenia, and mucositis, but none reached grade 3 or grade 4 in severity. Improvement of pain was observed in 17 patients (32.1%).. S-1 monotherapy provides active and safe salvage chemotherapy for patients with advanced gastric cancer who have been previously treated with paclitaxel and cisplatin.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Fever; Humans; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Pain; Salvage Therapy; Severity of Illness Index; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and gemcitabine combination regimen in the treatment of elderly patients (> or = 70 years) with advanced nonsmall cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC were treated with S-1 and gemcitabine. S-1 was administered orally twice daily for 14 days and gemcitabine on days 1 and 15 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 800/60; level 2, 1000/60; level 3, 1000/70; and level 4, 1000/80 [gemcitabine (mg/m2/ day)/S-1 (mg/m2/day)]. The dose-limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle. Sixteen patients were enrolled in this study. The main grade 3 toxicities observed during the first cycle were neutropenia (43.7%), leukopenia (18.7%), and hyperglycemia. One of six patients in level 3 had DLT. Although no patients in level 4 experienced DLT, this level was considered the maximum tolerated dose. Level 4 was selected as the recommended dose. Objective responses were seen in four patients (response rate, 42.9%). The combination of S-1 plus gemcitabine is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Female; Gemcitabine; Humans; Hyperglycemia; Leukopenia; Lung Neoplasms; Male; Maximum Tolerated Dose; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome

To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC).. Cisplatin was fixed at a dose of 60 mg/m2 on day 1 (D1) and the starting dose of S-1 was 60 mg/m2/day (30 mg/m2 bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m2 bid up to 100 mg/m2/day (level V) unless the MTD was achieved.. Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m2/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m2/day (N=23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6-6.0 months) with a median OS of 10.0 months (95% CI, 5.1-14.8 months). Grade 3-4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%).. The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Fever; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Stomach Neoplasms; Tegafur

Optimal chemotherapy for advanced biliary tract cancer (BTC) is yet to be defined. We carried out this study to evaluate the efficacy and toxicity of combination chemotherapy with S-1 and cisplatin in metastatic or relapsed BTC.. Patients with pathologically proven BTC were eligible. The chemotherapy regimen consisted of S-1 (40 mg/m(2) p.o. b.i.d. from D1-14) and cisplatin (60 mg/m(2) on D1), repeated every 3 weeks.. Fifty-one BTC patients (metastatic:relapsed = 37:14, Gall-bladder:intrahepatic bile ducts:extrahepatic bile ducts = 16:25:10) were enrolled from January 2005 to December 2006. Median age was 57 years (range, 31-71) and most patients had a good performance status. The overall response rate was 30% [95% confidence interval (CI), 17.3-42.7] and complete response was observed in two patients (4%), partial response in 13 (26%), stable disease in 21 (42%), and progressive disease in 9 (18%). With a median follow-up of 12.4 months, the median time to progression was 4.8 months (95% CI, 3.3-6.3) and median overall survival was 8.7 months (95% CI, 6.0-11.4). Major toxic effects were grade 3/4 neutropenia (8.9% of all cycles) and febrile neutropenia was observed in six cycles (2.7% of all cycles).. Combination chemotherapy with S-1 and cisplatin was a moderately effective outpatient-based regimen in BTC patients. Toxic effects were moderate but manageable.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cisplatin; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Salvage Therapy; Survival Analysis; Tegafur; Thrombocytopenia

A pre-clinical study demonstrated that paclitaxel induced thymidine phosphorylase in the tumor tissues. The combination of paclitaxel and doxifluridine is expected to exert extra anti-tumor effects. We evaluated the efficacy of this combination in patients with unresectable or recurrent gastric cancer who had been previously treated with S-1.. Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evaluation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m(2), iv on days 1 and 8; and doxifluridine, 600 mg/m(2), po on days 1-14. The treatment was repeated every three weeks. Primary endpoint was response rate (RR); and secondary endpoints were overall survival (OS), progression free survival (PFS) and onset rate of adverse events.. From September 2003 to March 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49-75 years); and performance status (PS) levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except two, clinical usefulness was evaluated resulting in RR of 18.2% (partial response, 6; stable disease, 15; progressive disease, 10; and not evaluable, 2 patients). Median survival time was 321 days and median PFS was 119 days. Severe adverse events were found in three patients to discontinue the present treatment.. The combination of paclitaxel and doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.

Topics: Adenocarcinoma; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Floxuridine; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

This Phase II study assessed the activity and safety of biweekly paclitaxel and oral S-1 as treatment for unresectable and recurrent gastric cancer. The maximum tolerated dose for this regimen had been established previously in a Phase I study performed in Japanese patients.. Chemotherapy was performed using two anticancer agents, S-1 and paclitaxel. Oral S-1 (80 mg/m(2)) was administered twice a day after meals for two consecutive weeks from Day 1 to 14, followed by a 2 week recovery period; paclitaxel (120 mg/m(2)) was administered intravenously, biweekly, on Days 1 and 15. The patient received cycles of this regimen every 4 weeks (q 28-day cycles). The primary end point was the response rate according to the Response Evaluation Criteria in Solid Tumors.. A total of 39 patients (median age, 65 years) were enrolled; 13 other patients were screened, but found to be ineligible. All patients had unresectable and recurrent gastric cancer. The most common treatment-related Grade 3/4 adverse events were neutropenia (37.5%), appetite loss, diarrhea, decreased sodium (each 5%), and anemia, increased alanine aminotransferase, general fatigue, and dizziness (each 2.5%). Almost all the patients experienced alopecia. Intent-to-treat analysis showed a response rate of 43.6%. With a median follow-up of 14 months (range 8-21 months), median survival was 256 days and the median time to progression was 4 months.. A combination regimen of biweekly paclitaxel and oral S-1 was well tolerated and showed promising activity against unresectable and recurrent gastric cancer.

Topics: Adenocarcinoma; Aged; Alopecia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Gastrointestinal Diseases; Humans; Hyponatremia; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur

The safety of chemotherapy combining TS-1 and weekly paclitaxel for the treatment of unresectable and recurrent gastric cancer was evaluated in this study. Paclitaxel was administered by intravenous drip infusion at a starting dose (level 1) of 50 mg/m2 on days 1, 8, and 15. TS-1 was administered orally at a dose of 40 mg/m2twice a day for 2 weeks (days 1-14) followed by 2 weeks rest. A total of 9 patients were enrolled in this study. Two out of 6 patients treated with level 1 suffered from leukocytopenia and neutropenia, which were determined as dose-limiting toxicity (DLT). Three patients were treated with level 2, in which the dose of paclitaxel was increased up to 60 mg/m2. One of 3 patients suffered from grade 3 diarrhea and one patient from grade 4 leukocytopenia, eutrocytopenia, anemia, and stomatitis, which were determined as DLT. According to these results,level 1 of this regimen was recommended as a safe treatment for gastric cancer patients. A phase II study will be performed to evaluate the efficacy of the combination chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

A 67-year-old man was admitted to our hospital, complaining of productive cough and chest pain. Chest radiograph and computed tomography revealed a huge mass invading the mediastinum, enlargement of right hilar and cardiophrenic lymph nodes and nodules in right lower lobe and left upper lobe. Multiple space occupying regions in the liver were also observed. Cytology for exfoliated sputum revealed adenocarcinoma, so he was diagnosed with advanced lung cancer (clinical stage T 4 N 2 M 1, stage IV). He was enrolled in a clinical phase II study, and received combination chemotherapy with TS-1 and cisplatin. TS-1 was administered on days 1-21. Cisplatin was administered on day 8. Every cycle was repeated every 5 weeks. The patient then received 6 cycles of chemotherapy,and yielded a partial response (87% decrease in size determined by RECIST criteria version 2. 0). Grade 2 leukopenia and neutropenia were observed, and non-hematologic toxicities were also mild. The disease progressed after the end of chemotherapy, and he was given 5 regimens of chemotherapy, including gefitinib. He died of brain metastases. Time to progression of his disease for combination chemotherapy using TS-1 and cisplatin chemotherapy was 240 days. Survival time was 709 days. This combination chemotherapy was effective in the present case, and might prolong survival. We think it is valuable to confirm the efficacy of TS-1 and cisplatin combination chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Leukopenia; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Pyridines; Tegafur

In the present article, we have summarized the phase I/II clinical trials on combination therapy of S-1 and docetaxel. With result of the phase I study, patients were treated with intravenous infusion of 40 mg/m2 docetaxel on day 1 and oral S-1 80 mg/m2/day on days 1 to 14 every 3 weeks. Forty eight patients received a total of 272 treatment cycles. No complete responses (CRs) and 27 partial responses (PRs) were observed for an overall response rate (CR+PR) of 56.2% (95% CI, 38-66%). Eighteen patients (37.5%) had stable disease (SD), and 3 patients (6.2%) had progressive disease (PD) as best response. The tumor control rate (CR+PR+SD) was 93.8% (95% CI, 83-98%). The median overall survival was 14.3 months (95% CI: 10.7-20.3 months) and the median time to tumor progression was 7.3 months (95% CI: 4.2-10.7 months). The most common grade 3-4 hematologic toxicities were neutropenia 58.3%, leukopenia 41.7%, febrile neutropenia 8.3%, and anemia 8.3%. The most common grade 3 nonhematologic toxicities were anorexia 14.6%, stomatitis 8.3%, nausea 6.3%, diarrhea 4.2%, constipation 4.2%, and vomiting 2.1%. No grade 4 nonhematologic toxicities were reported, and all treatment-related toxicities were resolved. The mechanisms underlying these synergistic effects of S-1 and docetaxel were examined by expression and activity analyses of 5-FU metabolic enzymes. The expressions of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were decreased and that of orotate phosphorybosyl transferase (OPRT) was increased in mRNA, protein level and activity assay after the treatment with docetaxel and 5-FU in the TMK-1 gastric cancer cell. These findings strongly indicate that the combination chemotherapy of docetaxel and S-1 is effective against gastric carcinomas and therefore is a good candidate as a standard chemotherapeutic strategy in treating these tumors.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Leukopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

We planned to conduct a phase II clinical study of combination therapy with CPT-11 and S-1. The antitumor effect was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20-75 years. Based on the results of our previous phase I/II study in patients with gastric cancer, the dosage was established in consideration of safety for outpatient therapy. CPT-11 was administered at a dose of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Interim analysis suggested excellent results, with a response rate of 50%. Combination therapy with CPT-11 and S-1 achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer.

Topics: Administration, Oral; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Irinotecan; Leukopenia; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Remission Induction; Tegafur

The standard care for unresectable locally advanced head and neck cancer (HNC) is concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT, a platinum-based regimen has shown a better survival benefit than other regimens. The control arm in a randomized trial for unresectable locally advanced HNC is radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been considered to be too toxic for clinical practice in Western countries and has required frequent dose modifications. Because the Japanese also have been considered unable to tolerate this regimen, no prospective study of it has been conducted in Japan. Most Japanese patients with locally advanced head and neck cancer have received concurrent chemoradiotherapy with 5-FU and CDDP (70-80 mg/m2). S-1 has shown high activity in HNC with a response rate of 34%. Furthermore, a combination of cisplatin and S-1 therapy for HNC has been reported to have good efficacy. With this rationale in mind, we conducted a phase I study of CRT with S-1 and CDDP for unresectable locally advanced squamous cell carcinoma of the head and neck. The CR rate was very promising, though preliminary, and warrants further investigation. The Japan Clinical Oncology Group (JCOG) is planning a multicenter phase II study of concurrent chemoradiotherapy with S-1 and CDDP for locally advanced unresectable HNC.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Radiation Injuries; Radiodermatitis; Radiotherapy Dosage; Tegafur

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who received no previous chemotherapy for advanced disease were enrolled in this study. Fifty nine patients (22 in stage IIIB and 37 in stage IV) were eligible for the evaluation of efficacy and safety. S-1 was orally administered twice daily after meals. Three doses of S-1 were prescribed according to body surface area (BSA), so that they would be approximately equivalent to 80 mg/m2/day. One cycle of S-1 consisted of consecutive administration for 28 days followed by a 2-week rest, and the cycle was repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59) (95% confidence interval: 12.3-34.7%). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all of the patients was 10.2 months (95% confidence interval: 7.7-14.5 months), and the one-year survival rate was 41.1%. S-1 was considered to be an active single agent against NSCLC.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Quality of Life; Remission Induction; Tegafur

We investigated preoperative chemotherapy with S-1 and low-dose cisplatin for the untreated stage II-IV oral squamous cell carcinoma patients. The chemotherapy consisted of S-1 80 mg/m2/day (day 1-14) and CDDP 5 mg/m2/day (day 1-5 and day 8-12) intravenous drip (less than 1 hour). In the second phase clinical trial of 44 patients, the clinical response rate was 63.7% and the histological response rate by the Oboshi-Shimosato's evaluation was 61.4%. The main adverse events were myelosuppression and gastrointestinal disturbance such as nausea 36.4%, anorexia 27.3%, neutropenia 25% and leukopenia 25%. Grade 3 and 4 adverse events were neutropenia 11.4%, leukopenia 9.1%, thrombocytopenia 4.5% and oligochromemia 4.5%. The two-year overall survival rate was 92.6%. The advantages of this chemotherapy are high response rate, low adverse effects and not to prevent planned therapies such as surgery and radiation. These facts suggest that this chemotherapy is suitable for preoperative chemotherapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Leukopenia; Male; Middle Aged; Mouth Neoplasms; Nausea; Neutropenia; Oxonic Acid; Preoperative Care; Survival Rate; Tegafur

A phase I/II clinical trial has been planned to evaluate the safety and efficacy of combination therapy of S-1 with low-dose cisplatin in patients with unresectable or recurrent gastric cancer. A new statistically as well as clinically deliberated study design is applied to determine the maximal benefits of combination chemotherapy. This trial uses a 'continual reassessment method' for evaluating toxicity and a "two-stage method" for assessing the response rate to determine the combination that achieves adequate tumor response without toxicity in a high proportion of patients. Three specialized institutions will recruit 10-16 patients for the phase I part of the trial, and 14 institutions, in conjunction with the three specialized ones, will enroll 42 patients for the phase II part. The goal of this trial is to establish a useful chemotherapeutic treatment in an outpatient setting.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Thrombocytopenia

A late phase II clinical study of S-1 against advanced or refractory breast cancer was done by 37 institutes in Japan. S-1 was administered twice daily at 80, 100 or 120 mg/body/day consecutively for 28 days followed by 14 days of rest (1 course). Eighty-three patients were enrolled and 81 were eligible for the study. The response ratio was 42.0% with 6 CR and 28 PR and its 95% confidence interval for the response was 31.1 to 53.5%. The median survival period was 910 days (95% confidence interval was 493-1, 083 days). The observed major adverse reactions (> or = grade 2) were as follows: hematological toxicities: leukopenia 21.0% (17/81), neutropenia 28.4% (23/81), erythropenia 4.9% (4/81); gastrointestinal toxicities: anorexia 9.9% (8/81), nausea and vomiting 12.3% (10/81), diarrhea 8.6% (7/81), stomatitis 1.2% (1/81), and fatigue 8.6% (7/81). The severe adverse reactions (> or = grade 3) were as follows; hematological toxicities: neutropenia 8.6% (7/81), anorexia 4.9% (4/81), fatigue 3.7% (3/81), nausea and vomiting 1.2% (1/81), diarrhea 1.2% (1/81), stomatitis 1.2% (1/81). Grade 4 adverse reactions (neutropenia and fatigue) were observed only in 1 patient. The ratio without hospitalization was 87.7%. These results strongly suggest the superior efficacy and safety of S-1 against patients suffering from advanced, refractory breast cancer. Therefore, S-1 may be a new therapeutic agent to prolong the survival period of breast cancer patients due to its high antitumor activity and low toxicity.

Topics: Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Breast Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Tegafur; Vomiting, Anticipatory

Irinotecan plus intravenous 5-fluorouracil with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative combining tegafur with the modulators 5-chloro-2,4-dihydroxypyrimidine (a potent dihydropyrimidine dehydrogenase inhibitor), and potassium oxonate (an orotate phosphoribosyl transferase inhibitor), in a molar ratio of 1 : 0.4 : 1. S-1 has a high response rate, of about 40%, in advanced gastric cancer. A phase I study was conducted to assess the maximum tolerated dose and the recommended dose of the combination of irinotecan and S-1.. Irinotecan was given intravenously over the course of 90 min on day 1 and S-1 was given orally from days 1 to 14 of a 21-day cycle. The dose of S-1 was 80 mg/m2 per day, given in two divided doses. The dose of irinotecan was escalated in a stepwise fashion from 100 mg/m2 (level 1; n = 3), to 125 mg/m2 (level 2; n = 3), and 150 mg/m2 (level 3; n = 6).. Dose-limiting toxicity did not occur during cycle 1, and the recommended dose for phase II studies was determined to be level 3, which was associated with grade 3 diarrhea in one patient, and with refusal to continue treatment because of prolonged fatigue in two patients. Grade 3 neutropenia developed in one of three patients at level 1 and level 2, and in two of six during cycle 1 of level 3. The recommended dose was determined to be 150 mg/m2 of irinotecan on day 1 and 80 mg/m2 per day of S-1 on days 1 to 14 of a 21-day cycle. Five of seven patients with measurable lesions had a partial response.. A combination of irinotecan and S-1 can be recommended for further phase II studies in patients with gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Fatigue; Female; Humans; Infusions, Intravenous; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety. S-1 was administered orally, twice daily, after meals. 3 dosages of S-1 were prescribed according to body surface area (BSA) so that they would be approximately equivalent to 80 mg m(-2)day(-1): BSA < 1.25 m(2), 40 mg b.i.d.; BSA> or =1.25 but <1.5 m(2); 50 mg b.i.d., and BSA> or =1.5 m(2): 60 mg b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days followed by a 2-week rest period, and cycles were repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59); (95% confidence interval: 12.3-34.7%). A PR was observed in 22.7% (5/22) of the stage IIIB patients and 21.6% (8/37) of the stage IV patients. The median response duration was 3.4 months (1.1-13.7 months or longer). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8% (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in 8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their incidences were relatively low. There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all patients was 10.2 months (95% confidence interval: 7.7-14.5 months), and the one-year survival rate was 41.1%. The MST of the stage IIIB patients was 7.9 months, and that of the stage IV patients was 11.1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47.4%, respectively. S-1 was considered to be an active single agent against NSCLC. Further study of S-1 with other active agents is warranted.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Survival Analysis; Tegafur; Treatment Outcome

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Remission Induction; Survival Analysis; Tegafur

In developing new anticancer agents, the most important thing is the balancing of antitumor activity and toxicity. To achieve high activity and low toxicity, S-1 was designed, in which tegafur, prodrug of 5-FU, was combined with two classes of modulators. CDHP, inhibitor of 5-FU degradation in liver and Oxo, inhibitor of 5-FU phosphoribosylation in digestive tract, respectively. This cooperative study with 15 nation-wide institutes was conducted to evaluate the antitumor activity and toxicity of S-1 in patients with advanced head and neck cancer from Jan. 1994 to March 1996 in Japan. Out of 26 patients, CR was achieved in 1 and PR in 11 with a response rate of 46.2%, while adverse events of grade 3 were as follows: hemoglobinemia (7.7%), leukocytopenia, neutropenia, stomatitis and anorexia (3.8%), each. Neither grade 4 adverse event nor treatment-related deaths were observed. Based on these findings, it was concluded that S-1 is a useful anticancer agent with the low grade toxicities for treatment of the patients with advanced head and neck cancer, and the effects of CDHP and Oxo found in preclinical studies might be also reflected in these results.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Stomatitis; Tegafur

There is no standard first-line chemotherapy for advanced gastric cancer with severe peritoneal metastasis. Although fluoropyrimidine is often used, its efficacy is limited, and it remains unclear whether combination therapy with platinum improves clinical outcomes.. This retrospective study involved patients at six Japanese academic hospitals between 2010 and 2016. Patients with advanced gastric cancer and severe peritoneal metastasis were included if they had massive ascites and/or inadequate oral intake requiring intravenous nutritional support. We then compared the efficacy and safety of fluoropyrimidine monotherapy with those of fluoropyrimidine/platinum combination therapy.. Compared with the combination therapy group (n = 64), the monotherapy group (n = 65) had worse general health (more patients with elderly age, performance status > 2, and having both massive ascites and inadequate oral intake). Both overall survival (9.0 vs 5.0 months, p < 0.01) and progression-free survival (4.3 vs 2.3 months, p < 0.01) were significantly longer in the combination group, and the significance remained after adjusting for prognostic variables (hazard ratios of 0.47 and 0.41, respectively; p < 0.01). Improvements in ascites and oral intake were also greater in the combination group. Although neutropenia (grade ≥ 3) occurred more frequently with combination therapy, both treatments in this study were tolerable.. Combination therapy with fluoropyrimidine and platinum might be more effective than monotherapy with fluoropyrimidine and was tolerable for patients with advanced gastric cancer and severe peritoneal metastasis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Malnutrition; Methotrexate; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Peritoneal Neoplasms; Progression-Free Survival; Pyridines; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome; Withholding Treatment; Young Adult

Gemcitabine has been standard of care in advanced pancreatic adenocarcinomas (PC) for almost two decades. Randomized, primarily Japanese, studies have shown promising efficacy when combined with S-1 (GemS-1); however, no data are published in Caucasian patients. We report the first study with a combination of GemS-1 in an unselected cohort of Caucasian PC patients.. In this observational cohort study, we analyzed efficacy and toxicity prospectively.. From July 2012 to July 2014, 64 patients received at least one cycle of GemS-1. 16 patients started therapy with gemcitabine and capecitabine (GemCap) but switched to GemS-1 after median 3 cycles of GemCap due to toxicity (hand-foot syndrome). 48 patients received GemS-1 as initial therapy. For the complete cohort, median age was 68 years (range 44-80); 22 patients (34%) had locally advanced PC; 42 patients (66%) had metastatic disease. Five patients had received prior adjuvant therapy with gemcitabine and 9 pts had received prior first-line therapy. The most common adverse event was fatigue (86%), however, only grade 3 in 3%. Five patients (8%) developed febrile neutropenia. Median PFS was 8.1 (95% CI 6.9-9.0) months and median OS was 11.7 (95% CI 10.7-13.1) months in the whole GemS-1 population. In the 48 patients starting with GemS-1, median PFS was 7.7 (95% CI 6.7-8.9) months and median OS was 11.5 (95% CI 9.7-12.3) months.. The combination of gemcitabine and S-1 is safe and associated with promising efficacy in a Caucasian population; however, this needs to be confirmed in prospective clinical trials.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Deoxycytidine; Diarrhea; Drug Combinations; Fatigue; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Treatment Outcome; White People

S-1 and cisplatin therapy (SP therapy) is widely used as the first-line of advanced/recurrent gastric cancer. However, severe neutropenia is often observed (40%) during this therapy. Therefore, the risk management of neutropenia is important. From September 2014 to April 2017, we investigated 76 patients who underwent SP therapy as primary treatment for advanced/recurrent gastric cancer at Ogaki Municipal Hospital. Risk factors for grade 3/4 neutropenia were examined by univariate and multivariate analyses. In SP therapy, 19 patients (25%) experienced grade 3/4 neutropenia. The results of multivariate analysis of factors with p <0.05 in the univariate analysis indicated that less than 10.6 g/dL of the haemoglobin value before the course at the lowest neutrophil count (odds ratio: 7.900; 95% CI: 1.280-48.60; p = 0.026), more than six courses of the total course (odds ratio: 9.13; 95% CI: 2.13-39.1; p = 0.003), and less than 3140 m2 neutrophil counts (odds ratio: 5.33; 95% CI: 1.47-19.3; p = 0.011) before chemotherapy were risk factors of grade 3/4 neutropenia. A low haemoglobin value before the course at the lowest neutrophil count was revealed as a risk factor causing severe neutropenia in SP therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Hemoglobins; Humans; Leukocyte Count; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Neutrophils; Oxonic Acid; Risk Factors; Stomach Neoplasms; Tegafur

The role of adjuvant chemotherapy has not yet been established for patients with resected biliary tract cancer. S-1 has been shown to exert activity against advanced biliary tract cancer. Therefore, we evaluated the feasibility of adjuvant chemotherapy with S-1 in patients with resected biliary tract cancer.. Patients with complete macroscopic resection of intrahepatic/extrahepatic bile duct, gall bladder, or ampullary cancer were eligible. S-1 was administered orally twice daily for 4 weeks every 6 weeks, up to 4 cycles. The treatment was continued up to 24 weeks or until recurrence/appearance of unacceptable toxicity. The primary endpoint was the treatment completion rate, which was defined as the percentage of patients who received a relative dose intensity of ≥ 75%. This trial was registered as UMIN000004051.. Thirty-three patients were enrolled between June 2010 and March 2011. The relative dose intensity was ≥ 75% in 27 patients representing a treatment completion rate of 81.8%. The most common grade 3/4 adverse event was neutropenia (18%). Grade 2 nausea or diarrhea was observed in 12%. The 3-year relapse-free survival rate was 39.4%. The 3-year survival rate was 54.5%.. Adjuvant chemotherapy with S-1 is feasible treatment in patients with resected biliary tract cancer. It is necessary to conduct a phase III study to confirm the efficacy of adjuvant therapy of S-1 in patients with resected BTC.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Biliary Tract Neoplasms; Carcinoma, Papillary; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Postoperative Period; Prognosis; Survival Rate; Tegafur; Young Adult

We report the case of a 72-year-old female who underwent laparoscopic total gastrectomy for gastric cancer. The pathological diagnosis was pT3, N1, M0, pStage II B. She received adjuvant chemotherapy with the TS-1®combination OD tablet, beginning 48 days after gastrectomy. The first course was stopped at day 7 because of neutropenia. The dose was decreased, a second course was started, and the patient completed her second course without neutropenia. After completion of the second course, we discovered that she had taken generic drugs(NKS-1®combination OD tablet)during the second course. She was enrolled in a clinical trial in which the administration of generic drugs was not permitted, as per the protocol. Beginning with the third course, we once again treated her with TS-1, and we observed a return of neutropenia in every subsequent course. We decreased the dose of TS-1 and changed the administration schedule each time. She exhibited no neutropenia only when using the generic S-1 formulation. It is possible that the anti-tumor effect of the generic S-1 formulation, and its associated adverse events, are not identical to the innovator formulation.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Drugs, Generic; Female; Gastrectomy; Humans; Neutropenia; Oxonic Acid; Stomach Neoplasms; Tegafur

Three randomised trials (GEST, JACCRO PC-01, and GEMSAP) were conducted to evaluate the efficacy of gemcitabine plus S-1 (GS) vs gemcitabine alone in patients with advanced pancreatic cancer (PC). In this pooled analysis, the efficacy and safety of GS vs gemcitabine were evaluated.. Additional follow-up was conducted and survival data were updated in each study. A total of 770 patients (gemcitabine 389; GS 381) were included in the pooled analysis. The efficacy and safety data were analysed according to disease extent: locally advanced PC (LAPC) or metastatic PC (MPC).. There were 738 (95.8%) overall survival events. In patients with LAPC (n=193), the median survival was 11.83 months for gemcitabine and 16.41 months for GS (hazard ratio (HR)=0.708; 95% confidence intervals (CI), 0.527-0.951; P=0.0220). In patients with MPC (n=577), the median survival was 8.02 months for gemcitabine and 9.43 months for GS (HR=0.872; 95% CI, 0.738-1.032; P=0.1102). The rate of grade 3/4 toxicity (rash and thrombocytopenia in LAPC; rash, diarrhoea, vomiting, and neutropaenia in MPC) was significantly higher for GS than for gemcitabine.. Gemcitabine plus S-1 is a viable treatment alternative to gemcitabine, which is one of the standard treatments in patients with LAPC.

Topics: Aftercare; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Deoxycytidine; Diarrhea; Drug Combinations; Drug Eruptions; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate; Tegafur; Thrombocytopenia; Vomiting

The use of adjuvant chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) has been shown to improve the outcome of patients with gastric cancer. There are limited data on the tolerability of S-1 in Chinese patients. In this multicentre retrospective study, we assessed the toxicity profile in local patients.. Patients with stage II-IIIC gastric adenocarcinoma who had undergone curative resection and who had received S-1 adjuvant chemotherapy were included in the study. Patient demographics, tumour characteristics, chemotherapy records, as well as biochemical, haematological, and other toxicity profiles were extracted from medical charts. Potential factors associated with grade 2-4 toxicities were identified.. Adjuvant S-1 was administered to 30 patients. Overall, 19 (63%) patients completed eight cycles. The most common grade 3-4 adverse events included neutropaenia (10%), anaemia (6.7%), septic episode (16.7%), diarrhoea (6.7%), hyperbilirubinaemia (6.7%), and syncope (6.7%). Dose reductions were made in 22 (73.3%) patients and 12 (40.0%) patients had dose delays. Univariate analyses showed that patients who underwent total gastrectomy were more likely to experience adverse haematological events (P=0.034). Patients with nodal involvement were more likely to report adverse non-haematological events (P=0.031). Patients with a history of regular alcohol intake were more likely to have earlier treatment withdrawal (P=0.044). Lower body weight (P=0.007) and lower body surface area (P=0.017) were associated with dose interruptions.. The tolerability of adjuvant S-1 in our patient population was similar to that in other Asian patient populations. The awareness of S-1-related toxicities and increasing knowledge of potential associated factors may enable optimisation of S-1 therapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anemia; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Hong Kong; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Retrospective Studies; Risk Factors; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

This study is aimed to assess the efficacy and toxicity of weekly liposome-paclitaxel and S-1 combination therapy as first-line treatment for advanced gastric cancer.. The chemotherapy regime was 80 mg/m(2) liposome-paclitaxel given on days 1, 8, 15 and 22, combined with S-1 60 mg (body surface area > 1.5) or 50 mg (1.25 < body surface area < 1.5) twice a day on days 1-28, 6 weeks as one cycle. The patients continued to be treated until they received four cycles or until they developed either progressive disease or untolerated toxicity. The response rate, progression-free survival, overall survival and toxicity were evaluated.. A total of 56 patients were enrolled, and the median age was 60 years (range = 38-70 years; 39 males and 17 females). The response rate and disease control rate were 25% (14/56) and 87.5% (49/56), respectively. The median progression-free survival was 6.1 months (95% confidence interval: 5.0-7.2), and the median overall survival was 10.6 months (95% confidence interval: 7.2-14.0). The most frequent hematological toxicities were neutropenia and anemia, which occurred in 22 (48.9%) and 11 (19.6%) patients, respectively.. The weekly administration of a combined regimen of liposome-paclitaxel plus S-1 is effective and has a favorable toxicity profile for advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Liposomes; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

The aim of this study was to evaluate S-1 and oxaliplatin combination chemotherapy (SOX) in patients with refractory pancreatic cancer (PC).. Consecutive patients with advanced PC refractory to gemcitabine who were treated with oral S-1 (80 mg/m²) on days 1-14 and intravenous oxaliplatin (100 mg/m²) on day 1 every 3 weeks were studied retrospectively. The primary end point was the objective response rate (ORR). The secondary end points were progression-free survival (PFS), overall survival (OS), the disease control rate (DCR), and safety.. Between March 2009 and October 2011, 30 patients were treated with SOX, with a median of two courses (range 1-8). The ORR and DCR were 10.0 and 50.0 %, respectively. Median PFS and OS were 3.4 months (95 % confidence interval [CI] 1.3-5.3) and 5.0 months (95 % CI 3.4-7.4), respectively. The median PFS and OS were 5.6 and 9.1 months in patients receiving S-1 and oxaliplatin as a second-line treatment. Major grade 3 or 4 adverse events included neutropenia (10.0 %), anemia (3.3 %), and diarrhea (6.7 %).. SOX was well tolerated and moderately effective in patients with refractory PC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Follow-Up Studies; Humans; Incidence; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Retrospective Studies; Salvage Therapy; Survival Analysis; Tegafur; Tokyo

The combination of oxaliplatin and S-1 is effective in patients with advanced gastric cancer. The purpose of this study was to analyze the safety and compliance of this combination regimen as adjuvant chemotherapy in patients with gastric cancer.. Clinical data of 71 patients with gastric cancer treated with oxaliplatin plus S-1 as adjuvant chemotherapy in the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) from Jan 1(st), 2010 to Jan 1(st), 2012 were retrospectively reviewed. The types and incidence rate of adverse events related to chemotherapy and the results of follow up of the patients were analyzed.. Among the 71 cases, 17 were treated with oxaliplatin biweekly, while 54 with oxaliplatin triweekly. The most common adverse events were neutropenia (n = 49, 69.0%), nausea/vomiting (n = 51, 71.8%), and anorexia (n = 49, 69.0%). The most frequent grade 3-4 toxicities were neutropenia (n = 13, 18.3%), thrombocytopenia (n = 10, 14.1%), anorexia (n = 5, 7.0%) and nausea/vomiting (n = 4, 5.6%). Seven (87.5%) of the 8 patients previously treated with neoadjuvant chemotherapy experienced thrombocytopenia in the postoperative adjuvant chemotherapy, and four (50%) of the 8 patients experienced grade 3-4 thrombocytopenia. The rates of grade 3-4 adverse events in patients aged 65-years or older were similar to that in younger patients.. The combination of oxaliplatin and S-1 used as adjuvant chemotherapy is well tolerated by patients with gastric cancer. Neutropenia, thrombocytopenia, nausea/vomiting and anorexia are the major treatment-related adverse events. Patients who received neoadjuvant chemotherapy do not well tolerate this regimen as postoperative adjuvant chemotherapy. This combination regimen has a manageable tolerability profile in adjuvant setting in patients ≥ 65 years old.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

The purpose of this study was to evaluate the effectiveness and adverse events of combination chemotherapy with oral S-1 administration following docetaxel (DOC) treatment by superselective intra-arterial infusion as neo-adjuvant chemotherapy (NAC) for patients with oral squamous cell carcinoma. Thirteen patients were enrolled in this study (9 men and 4 women, with a mean age of 61. 0 years). All patients were given S-1 65mg/m(2) per day for 14 days, and DOC 40-50mg/m(2) by intraarterial infusion was administered. The locoregional response evaluated 3 weeks after administration was 100%, including a 69. 2% complete response. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that 3 cases were Grade II a, 4 cases Grade II b, 1 case Grade IV a, and 4 cases Grade IV c. The severe side effects were neutropenia and cerebral infarction. The present study suggests that combination chemotherapy with S-1 and DOC by superselective intra-arterial infusion would be an effective and safe regimen in NAC for oral squamous cell carcinomas.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cerebral Infarction; Docetaxel; Drug Combinations; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Neutropenia; Oxonic Acid; Taxoids; Tegafur

We analyzed the clinical efficacy of pre-operative combination chemotherapy using docetaxel, cisplatin and S-1 for advanced gastric cancer. Four patients were enrolled and staging laparoscopy was performed. Patients received intravenous docetaxel and cisplatin (35 mg/m2) on day 1 and 15, and oral S-1 80 mg/m2 on day 1-14 every 4 weeks. Two patients received two courses of chemotherapy and two patients received three courses of chemotherapy. Neutropenia of more than grade 3 was found in 3 cases. All cases were PR on preoperative imaging. Curative operation was performed on three cases. Histological anti-tumor effect was judged to be grade 2 in 1 case and grade 1a in 3 cases. In the postoperative period, all patients received S-1-based adjuvant chemotherapy. The combination chemotherapy using docetaxel, cisplatin and S-1 plus operation was a candidate for the standard treatment strategy for advanced gastric cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neutropenia; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy on metastatic gastric cancer.. Docetaxel and oxaliplatin were administered intravenously on day 1 and S-1 was administered orally on days 1-14 of every 21-day cycle. The doses of docetaxel/oxaliplatin/S-1 in the phase I study were level -1A, 52.5/80/60 mg/m(2); level -1B, 52.5/80/80 mg/m(2); level 1A, 52.5/105/80 mg/m(2); level 1B, 52.5/130/80 mg/m(2); level 2A, 60/105/80 mg/m(2); level 2B, 60/130/80 mg/m(2); level 3A, 67.5/105/80 mg/m(2); level 3B, 67.5/130/80 mg/m(2); level 4A, 75/105/80 mg/m(2); level 4B, 75/130/80 mg/m(2).. Nine patients were enrolled. One of six patients at level 1A and two of three patients at level 1B developed dose-limiting toxicity (febrile neutropenia) during the initial two cycles. Therefore, the doses used at levels 1B and 1A were defined as the MTD and RD, respectively. All patients were evaluated for toxicity and response. Six partial responses were noted, and the overall response rate was 67%.. The RD of the DOS regimen in patients with advanced gastric cancer was docetaxel 52.5 mg/m(2) and oxaliplatin 105 mg/m(2) on day 1 and S-1 80 mg/m(2) on days 1-14 of every 21-day cycle. A phase II study using the RD is currently underway.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Gastrectomy; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The efficacy of S-1 as part of a 2nd/3rd-line therapy in cases of advanced recurrent colon cancer was studied.. The efficacy of treatment with S-1 (initial dosage: 80 mg/m(2)) was studied in 19 patients with advanced recurrent colon cancer in whom PD was observed after pretreatment with 5-FU-based combination chemotherapy had been performed during the period from December 2003 to April 2006. Patients who underwent a course that exceeded 1 month after the pretreatment and who met the criteria for the appropriate use of S-1 were selected as subjects.. The median age was 65 years (45 to 75 years old) with 10, 6, and 3 patients having a PS score of 0, 1, and 2, respectively, and the details of the duration of the pretreatment was that 12 and 7 patients respectively received 2nd-and 3rd-line therapy. The median duration of the treatment with S-1 was 141 days, and the number of subjects with PR, SD, and PD who underwent S-1 treatment was 2, 7, and 6, respectively, with a response rate of 13. 3% and a disease control rate of 60. 0%. The progression free survival time and the overall median survival time were 5. 4 months and 13. 9 months, respectively. Regarding the effectiveness according to treatment line, particularly in the subjects who were administered S-1 as part of the 2nd-line therapy, good results were observed, thus showing a response rate of 20% and an overall median survival time of 13. 9 months, which exceeded 1 year. The incidence of adverse events was 58%(11 and 19), and the major side effects were neutropenia in 31. 6% (6 and 19) and leukopenia in 21. 1% (4 and 19) of the patients, which are both mild and showed a grade of 2 or lower.. The use of S-1 as part of a 2nd/3rd-line therapy in cases of advanced recurrent colon cancer may contribute to good prognoses.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Disease Progression; Drug Combinations; Female; Humans; Japan; Leukopenia; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Prognosis; Recurrence; Salvage Therapy; Survival Rate; Tegafur

Myelosuppression that occurs during chemotherapy has been reported to be a predictor of better survival in patients with breast or lung carcinomas. We evaluated the prognostic implications of chemotherapy-induced neutropenia in advanced gastric carcinoma. Data from a prospective survey of oral fluoropyrimidine S-1 for advanced gastric cancer patients in Japan were reviewed. We identified 1055 untreated patients with adequate baseline bone marrow function. During treatment with S-1, a total of 293 (28%) patients experienced grade 1 or higher neutropenia. The adjusted hazard ratio of death for the presence of neutropenia, as compared with the absence of such toxicity, from a multivariate Cox model was 0.72 (95% confidence interval, 0.54-0.95; P=0.0189) for grade 1 neutropenia, 0.63 (0.50-0.78; P<0.0001) for grade 2 neutropenia and 0.71 (0.51-0.98; P=0.0388) for grade 3-4 neutropenia. These findings suggest that the occurrence of neutropenia during chemotherapy is an independent predictor of increased survival in patients with advanced gastric cancer, whereas the absence of such toxicity indicates that the dosages of drugs are not pharmacologically adequate. Monitoring of neutropenia in patients who receive chemotherapy may contribute to improved drug efficacy and favourable survival.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Male; Middle Aged; Neutropenia; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Analysis; Tegafur

We experienced a case of good response in acute respiratory distress syndrome (ARDS) treated with sivelestat sodium hydrate during chemotherapy for cholangiocarcinoma. A 66-year-old male treated with combined paclitaxel (PTX) and S-1 suffered from ARDS following neutropenia. Sputum and blood culture examinations demonstrated an unknown origin, so sivelestat sodium hydrate was considered more effective than antibiotics. Sivelestat sodium hydrate ought to be used for ARDS treatment even during administration of anti-cancer agent.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Drug Administration Schedule; Drug Combinations; Glycine; Humans; Male; Neutropenia; Oxonic Acid; Paclitaxel; Respiratory Distress Syndrome; Serine Proteinase Inhibitors; Sulfonamides; Tegafur

As a measure to ensure safe use of TS-1 during the early marketing period, a drug use investigation was conducted on an all-case basis. Extra safety monitoring,rarely included in the use investigation,was also planned for patients who began therapy with this agent. Of the 4,177 subjects registered during the year beginning in March 1999, 3,882 started TS-1 therapy. Aside from 74 dropouts, 3,808 cases were evaluable for safety. The overall incidence of adverse reactions, with high frequencies of myelosuppression and gastrointestinal disorders, was 74.3%: a result similar to an incidence of 77.5% (100/129) found in the early phase II trial with gastric cancer patients. Safety monitoring made it possible to check if a given patients was eligible for proper use before treatment is begun. During TS-1 administration,collaboration was formed between physicians and medical representatives to ensure regular laboratory testing and to check the test findings. Measures were considered necessary to secure the safe use of drugs with manifest risk of serious adverse reactions, such as antineoplastic agents, during the initial period of market introduction. Our present approach proved effective as one of such measures.

Topics: Antimetabolites, Antineoplastic; Capsules; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Humans; Leukopenia; Neutropenia; Oxonic Acid; Product Surveillance, Postmarketing; Pyridines; Registries; Stomach Neoplasms; Tegafur; Thrombocytopenia

The aim of this survey was to confirm the safety and efficacy of S-1 for advanced gastric cancer after market release.. All patients had to be registered with the manufacturer for a post-marketing survey, according to the government recommendation. All patients were monitored for safety and survival.. During this survey, a total of 4,177 patients with advanced gastric cancer were registered. The incidences of all adverse events and of grade 3 or worse events in the 3,808 patients evaluable for safety were 74% and 25%, respectively. In patients with lower creatinine clearance at baseline, the incidences of adverse reactions were higher for all grades combined, as well as for grade 3 or worse. There were 90 (2.4%) early deaths (within 30 days of the initiation of the treatment) and 5 (0.1%) deaths possibly related to the treatment. The median survival time and the 1-year survival rate for all patients evaluable for efficacy (n=3,801) were 8.3 months (95% CI: 8.0-8.6 months) and 33.3% (95% CI: 31.8-34.9%), respectively.. This nationwide survey confirmed that the safety and efficacy profiles of S-1 were similar to those seen in the registration study.

Topics: Aged; Anorexia; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Female; Humans; Japan; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Product Surveillance, Postmarketing; Registries; Stomach Neoplasms; Survival Rate; Tegafur

We report a case of non-curatively resected gastric cancer successfully treated with TS-1 and irinotecan (CPT-11) combination therapy, resulting in long-term survival of 17 months. A 56-year-old woman underwent noncurative resection with total gastrectomy for advanced gastric cancer with severe lymph node metastasis on June 3, 2004. Postoperatively, She received TS-1 and CPT-11 combination therapy (TS-1 80 mg/m(2) day 1-21, CPT-11 80 mg/m(2) day 1, 15, every 5 weeks). However, due to grade 4 neutropenia, and grade 3 nausea and anorexia in the first course, both doses were reduced. Since then, no grade 3 or severer adverse reactions have been observed. After 5 courses, partial response to lymph node metastasis was obtained, and her quality of life was improved. Thus, TS-1 and CPT-11 combination therapy has been effective for 17 months, suggesting that it is promising for long-term administration and survival to continue it perseveringly.

Topics: Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Irinotecan; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Quality of Life; Stomach Neoplasms; Survivors; Tegafur

We report a patient with chemotherapy-naïve advanced pancreatic cancer having multiple liver metastases which dramatically responded to S-1, an oral fluoropyrimidine. The patient was enrolled in the "Late Phase II Clinical Study of S-1 in Patients with Advanced Pancreatic Cancer." Anti-tumor efficacy after the first four courses of S-1 monotherapy was confirmed to be partial response (PR) in overall response by Response Evaluation Criteria in Solid Tumors (RECIST). Grade 3 neutropenia was observed, but no other severe toxicities were noted. On the basis of the results of the late phase II clinical study, S-1 is a promising agent for systemic chemotherapy against advanced pancreatic cancers because of its excellent efficacy, high tolerability, and convenient route of oral administration.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Clinical Trials, Phase II as Topic; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Liver Neoplasms; Middle Aged; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Tomography, X-Ray Computed

The effects of haematological adverse events on the prognosis of patients with gastric cancer were investigated.. We retrospectively analysed the association between haematological adverse events and prognosis in 23 patients with far advanced or recurrent gastric cancer treated with a JFMC27-9902 regimen consisting of an oral fluorouracil derivative S-1 plus low-dose cisplatin.. The patients who suffered grade 2-3 neutropenia (n = 10; median survival time [MST] 679 days) were found to have significantly more favourable prognoses than patients who developed grade 0-1 (n = 10; MST 271 days) or grade 4 neutropenia (n = 3; MST 408 days) (P = 0.0039 and 0.0112, respectively), although no significant differences were found among the clinicopathological factors of any grade groups. With respect to anaemia or thrombocytopenia, there were no significant differences among the MSTs of the groups stratified by toxicity grade. Multivariate survival analysis revealed that grade 2-3 neutropenia is an independent predictor of a more favourable prognosis (hazard ratio = 38.693, P = 0.0004).. These results suggest that S-1 plus low-dose cisplatin against gastric cancer may contribute to long survival when it induces moderate neutropenia.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Multivariate Analysis; Neutropenia; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Time Factors

We investigated the histological response and toxicities of combination chemotherapy with TS-1 and low-dose CDDP, and evaluated the usefulness of this regimen as a preoperative chemotherapy. Fourteen patients were enrolled in this study (two men and 12 women, with a mean age of 54.5 years). Patients were administered TS-1 80 mg/m2/day (days 1-14) and CDDP 5 mg/m2/day (days 1-5, 8-12) and followed by radical surgery or biopsy within 2 weeks. Ten patients completed 1 cycle of chemotherapy, two received 0.5 cycle and two others 1.5 cycle. The histological antitumor effects were evaluated with Ohboshi & Shimosato's classification using surgical or biopsy specimens of primary tumors. The response rate was 64.3% in clinical evaluation and 50.0% in histological evaluation. The number of patients who showed CR were 7/14 (50.0%) and 5/14 (35.7%) by histological and clinical evaluation, respectively. Two patients showed grade 3 neutropenia. Almost all patients revealed no or mild toxicities. TS-1 with low-dose CDDP represents a highly effective antitumor activity and mild toxicities. Especially, the CR rate was very high. These data suggested that this regimen was useful to avoid surgery or to realize minimal surgery for oral squamous cell carcinoma patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Neutropenia; Oxonic Acid; Pyridines; Tegafur

We report a case of right maxillary carcinoma with metastases to the cervical lymph nodes (T4N2cM0, Stage IV). A 76-year-old woman was administered preoperative chemoradiotherapy, followed by curative surgery. TS-1 (80 mg/day), CDDP (5 mg/m2/day) and concurrent radiation (total 40 Gy) induced a complete response. Grade 2 neutropenia, thrombocytopenia and stomatitis were observed. In the primary tumor and cervical metastatic lymph nodes, no viable carcinoma cells were detected and cancer nests were replaced with marked fibrous tissue.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Maxillary Neoplasms; Neck; Neutropenia; Oxonic Acid; Pyridines; Radiotherapy, Adjuvant; Stomatitis; Tegafur; Thrombocytopenia

To examine the adverse reactions to TS-1 for patients with recurrent head and neck cancer, five patients with locoregional recurrences and two with distant metastasis were enrolled in the present study and took TS-1 as outpatients. All patients underwent irradiation with or without surgery before administration of TS-1. One patient was given 100 mg of TS-1 daily, and six patients were given 120 mg of TS-1 daily. Thirteen courses consisted of the regimen of four weeks of TS-1 administration followed by two weeks of intermission, nine courses consisted of the regimen of two weeks of administration followed by one week of intermission, and seven courses consisted of the regimen of two weeks of administration followed by two weeks of intermission. Anemia, leukopenia, neutropenia, and liver dysfunction were often observed as adverse reactions to TS-1 administration. Grade 3 bilirubinemia was observed in only one course, but other adverse reactions consisted of grade 1 or grade 2. Almost all adverse reactions returned to normal after the cessation of drug administration. Based on these results, we conclude that TS-1 is a safe drug for the treatment of outpatients with recurrent head and neck cancer.

Topics: Adult; Aged; Ambulatory Care; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Head and Neck Neoplasms; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Tegafur